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CHEMICAL ENGINEERING (188 journals)                     

Showing 1 - 0 of 0 Journals sorted alphabetically
AATCC Journal of Research     Full-text available via subscription   (Followers: 4)
ACS Sustainable Chemistry & Engineering     Hybrid Journal  
Acta Crystallographica Section B: Structural Science, Crystal Engineering and Materials     Hybrid Journal   (Followers: 4)
Acta Polymerica     Hybrid Journal   (Followers: 7)
Additives for Polymers     Full-text available via subscription   (Followers: 20)
Adhesion Adhesives & Sealants     Hybrid Journal   (Followers: 6)
Advanced Chemical Engineering Research     Open Access   (Followers: 27)
Advanced Powder Technology     Hybrid Journal   (Followers: 13)
Advances in Applied Ceramics     Hybrid Journal   (Followers: 4)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 23)
Advances in Chemical Engineering and Science     Open Access   (Followers: 50)
Advances in Polymer Technology     Hybrid Journal   (Followers: 12)
African Journal of Pure and Applied Chemistry     Open Access   (Followers: 7)
Annual Review of Analytical Chemistry     Full-text available via subscription   (Followers: 9)
Annual Review of Chemical and Biomolecular Engineering     Full-text available via subscription   (Followers: 9)
Anti-Corrosion Methods and Materials     Hybrid Journal   (Followers: 6)
Applied Petrochemical Research     Open Access   (Followers: 2)
Asia-Pacific Journal of Chemical Engineering     Hybrid Journal   (Followers: 7)
Biochemical Engineering Journal     Hybrid Journal   (Followers: 13)
Biofuel Research Journal     Open Access   (Followers: 3)
Biomass Conversion and Biorefinery     Partially Free   (Followers: 11)
Brazilian Journal of Chemical Engineering     Open Access   (Followers: 3)
Bulletin of Chemical Reaction Engineering & Catalysis     Open Access   (Followers: 2)
Bulletin of the Chemical Society of Ethiopia     Open Access   (Followers: 3)
Carbohydrate Polymers     Hybrid Journal   (Followers: 7)
Catalysts     Open Access   (Followers: 6)
ChemBioEng Reviews     Full-text available via subscription  
Chemical and Engineering News     Free   (Followers: 11)
Chemical and Materials Engineering     Open Access   (Followers: 6)
Chemical and Petroleum Engineering     Hybrid Journal   (Followers: 10)
Chemical and Process Engineering     Open Access   (Followers: 20)
Chemical and Process Engineering Research     Open Access   (Followers: 18)
Chemical Engineering & Technology     Hybrid Journal   (Followers: 33)
Chemical Engineering and Processing: Process Intensification     Hybrid Journal   (Followers: 17)
Chemical Engineering and Science     Open Access   (Followers: 13)
Chemical Engineering Communications     Hybrid Journal   (Followers: 12)
Chemical Engineering Journal     Hybrid Journal   (Followers: 27)
Chemical Engineering Research and Design     Hybrid Journal   (Followers: 21)
Chemical Engineering Research Bulletin     Open Access   (Followers: 8)
Chemical Engineering Science     Hybrid Journal   (Followers: 20)
Chemical Geology     Hybrid Journal   (Followers: 14)
Chemical Papers     Hybrid Journal   (Followers: 2)
Chemical Product and Process Modeling     Hybrid Journal   (Followers: 3)
Chemical Reviews     Full-text available via subscription   (Followers: 128)
Chemical Society Reviews     Full-text available via subscription   (Followers: 39)
Chemical Technology     Open Access   (Followers: 11)
ChemInform     Hybrid Journal   (Followers: 4)
Chemistry & Industry     Hybrid Journal   (Followers: 3)
Chemistry Central Journal     Open Access   (Followers: 5)
Chemistry of Materials     Full-text available via subscription   (Followers: 144)
Chemometrics and Intelligent Laboratory Systems     Hybrid Journal   (Followers: 15)
ChemSusChem     Hybrid Journal   (Followers: 5)
Chinese Chemical Letters     Full-text available via subscription   (Followers: 3)
Chinese Journal of Chemical Engineering     Full-text available via subscription   (Followers: 3)
Chinese Journal of Chemical Physics     Hybrid Journal   (Followers: 1)
Coke and Chemistry     Hybrid Journal   (Followers: 1)
Coloration Technology     Hybrid Journal  
Computational Biology and Chemistry     Hybrid Journal   (Followers: 9)
Computer Aided Chemical Engineering     Full-text available via subscription   (Followers: 1)
Computers & Chemical Engineering     Hybrid Journal   (Followers: 9)
CORROSION     Full-text available via subscription   (Followers: 19)
Corrosion Engineering, Science and Technology     Hybrid Journal   (Followers: 35)
Corrosion Reviews     Hybrid Journal   (Followers: 3)
Crystal Research and Technology     Hybrid Journal   (Followers: 5)
Current Opinion in Chemical Engineering     Open Access   (Followers: 7)
Education for Chemical Engineers     Hybrid Journal   (Followers: 4)
Eksergi     Open Access  
Emerging Trends in Chemical Engineering     Full-text available via subscription  
European Polymer Journal     Hybrid Journal   (Followers: 40)
Fibers and Polymers     Full-text available via subscription   (Followers: 4)
Fluorescent Materials     Open Access   (Followers: 1)
Focusing on Modern Food Industry     Open Access   (Followers: 2)
Frontiers of Chemical Science and Engineering     Hybrid Journal   (Followers: 1)
Gels     Open Access  
Geochemistry International     Hybrid Journal   (Followers: 2)
Handbook of Powder Technology     Full-text available via subscription   (Followers: 3)
Heat Exchangers     Open Access   (Followers: 1)
High Performance Polymers     Hybrid Journal  
Hungarian Journal of Industry and Chemistry     Open Access  
Indian Chemical Engineer     Hybrid Journal   (Followers: 5)
Indian Journal of Chemical Technology (IJCT)     Open Access   (Followers: 9)
Indonesian Journal of Chemical Science     Open Access  
Industrial & Engineering Chemistry     Full-text available via subscription   (Followers: 9)
Industrial & Engineering Chemistry Research     Full-text available via subscription   (Followers: 20)
Industrial Chemistry Library     Full-text available via subscription   (Followers: 3)
Industrial Gases     Open Access  
Info Chimie Magazine     Full-text available via subscription   (Followers: 3)
International Journal of Chemical and Petroleum Sciences     Open Access   (Followers: 2)
International Journal of Chemical Engineering     Open Access   (Followers: 6)
International Journal of Chemical Reactor Engineering     Hybrid Journal   (Followers: 2)
International Journal of Chemical Technology     Open Access   (Followers: 5)
International Journal of Chemoinformatics and Chemical Engineering     Full-text available via subscription   (Followers: 2)
International Journal of Food Science     Open Access   (Followers: 3)
International Journal of Industrial Chemistry     Open Access  
International Journal of Polymeric Materials     Hybrid Journal   (Followers: 5)
International Journal of Science and Engineering     Open Access   (Followers: 4)
International Journal of Waste Resources     Open Access   (Followers: 3)
Journal of Chemical Engineering & Process Technology     Open Access   (Followers: 4)
Journal of Applied Crystallography     Hybrid Journal   (Followers: 5)
Journal of Applied Electrochemistry     Hybrid Journal   (Followers: 10)
Journal of Applied Polymer Science     Hybrid Journal   (Followers: 103)
Journal of Biomaterials Science, Polymer Edition     Hybrid Journal   (Followers: 9)
Journal of Bioprocess Engineering and Biorefinery     Full-text available via subscription  
Journal of Chemical & Engineering Data     Full-text available via subscription   (Followers: 10)
Journal of Chemical and Biological Interfaces     Full-text available via subscription   (Followers: 1)
Journal of Chemical Ecology     Hybrid Journal   (Followers: 6)
Journal of Chemical Engineering     Open Access   (Followers: 13)
Journal of Chemical Engineering and Materials Science     Open Access   (Followers: 2)
Journal of Chemical Science and Technology     Open Access   (Followers: 4)
Journal of Chemical Sciences     Partially Free   (Followers: 17)
Journal of Chemical Technology & Biotechnology     Hybrid Journal   (Followers: 10)
Journal of Chemical Theory and Computation     Full-text available via subscription   (Followers: 15)
Journal of CO2 Utilization     Hybrid Journal   (Followers: 2)
Journal of Crystallization Process and Technology     Open Access   (Followers: 7)
Journal of Environmental Chemical Engineering     Hybrid Journal   (Followers: 3)
Journal of Food Measurement and Characterization     Hybrid Journal  
Journal of Food Processing & Technology     Open Access  
Journal of Fuel Chemistry and Technology     Full-text available via subscription   (Followers: 4)
Journal of Geochemical Exploration     Hybrid Journal   (Followers: 1)
Journal of Industrial and Engineering Chemistry     Hybrid Journal   (Followers: 1)
Journal of Information Display     Hybrid Journal  
Journal of Inorganic and Organometallic Polymers and Materials     Partially Free   (Followers: 7)
Journal of Modern Chemistry & Chemical Technology     Full-text available via subscription   (Followers: 2)
Journal of Molecular Catalysis A: Chemical     Hybrid Journal   (Followers: 5)
Journal of Non-Crystalline Solids     Hybrid Journal   (Followers: 7)
Journal of Organic Semiconductors     Open Access   (Followers: 4)
Journal of Physics and Chemistry of Solids     Hybrid Journal   (Followers: 5)
Journal of Polymer and Biopolymer Physics Chemistry     Open Access   (Followers: 4)
Journal of Polymer Engineering     Hybrid Journal   (Followers: 8)
Journal of Polymer Research     Hybrid Journal   (Followers: 6)
Journal of Polymer Science Part C : Polymer Letters     Hybrid Journal   (Followers: 5)
Journal of Polymers     Open Access   (Followers: 2)
Journal of Polymers and the Environment     Hybrid Journal   (Followers: 1)
Journal of Pure and Applied Chemistry Research     Open Access   (Followers: 1)
Journal of the American Chemical Society     Full-text available via subscription   (Followers: 246)
Journal of the Bangladesh Chemical Society     Open Access  
Journal of the Brazilian Chemical Society     Open Access   (Followers: 2)
Journal of The Institution of Engineers (India) : Series E     Hybrid Journal   (Followers: 1)
Journal of the Pakistan Institute of Chemical Engineers     Open Access   (Followers: 1)
Journal of the Taiwan Institute of Chemical Engineers     Hybrid Journal   (Followers: 2)
Journal of Water Chemistry and Technology     Hybrid Journal   (Followers: 8)
Jurnal Bahan Alam Terbarukan     Open Access  
Jurnal Inovasi Pendidikan Kimia     Open Access  
Jurnal Reaktor     Open Access  
Jurnal Teknologi Dan Industri Pangan     Open Access   (Followers: 1)
Korean Journal of Chemical Engineering     Hybrid Journal   (Followers: 3)
Main Group Metal Chemistry     Hybrid Journal   (Followers: 1)
Materials Chemistry and Physics     Full-text available via subscription   (Followers: 14)
Materials Science and Applied Chemistry     Open Access  
Materials Sciences and Applied Chemistry     Full-text available via subscription  
Modern Chemistry & Applications     Open Access  
Molecular Imprinting     Open Access  
Nanocontainers     Open Access  
Nanofabrication     Open Access  
Noise Control Engineering Journal     Full-text available via subscription   (Followers: 2)
Ochrona Srodowiska i Zasobów Naturalnych : Environmental Protection and Natural Resources     Open Access  
Petroleum Chemistry     Hybrid Journal   (Followers: 1)
Physics and Chemistry of Glasses - European Journal of Glass Science and Technology Part B     Full-text available via subscription   (Followers: 3)
Plasma Processes and Polymers     Hybrid Journal  
Plasmas and Polymers     Hybrid Journal  
Polymer     Hybrid Journal   (Followers: 106)
Polymer Bulletin     Hybrid Journal   (Followers: 7)
Polymer Composites     Hybrid Journal   (Followers: 13)
Polyolefins Journal     Open Access  
Powder Technology     Hybrid Journal   (Followers: 12)
Recyclable Catalysis     Open Access   (Followers: 1)
Research on Chemical Intermediates     Hybrid Journal  
Reviews in Chemical Engineering     Hybrid Journal   (Followers: 5)
Revista Cubana de Química     Open Access  
Revista ION     Open Access  
Revista Mexicana de Ingeniería Química     Open Access  
Rubber Chemistry and Technology     Full-text available via subscription   (Followers: 2)
Russian Chemical Bulletin     Hybrid Journal   (Followers: 2)
Russian Journal of Applied Chemistry     Hybrid Journal   (Followers: 1)
Science and Engineering of Composite Materials     Hybrid Journal   (Followers: 57)
Solid Fuel Chemistry     Hybrid Journal  
South African Journal of Chemical Engineering     Open Access   (Followers: 2)
South African Journal of Chemistry     Open Access   (Followers: 2)
Surface Engineering and Applied Electrochemistry     Hybrid Journal   (Followers: 5)
Sustainable Chemical Processes     Open Access   (Followers: 2)
Synthesis Lectures on Chemical Engineering and Biochemical Engineering     Full-text available via subscription  
The Canadian Journal of Chemical Engineering     Hybrid Journal   (Followers: 3)
The Chemical Record     Hybrid Journal   (Followers: 1)
Theoretical Foundations of Chemical Engineering     Hybrid Journal   (Followers: 2)
Transition Metal Chemistry     Hybrid Journal   (Followers: 2)
Transylvanian Review of Systematical and Ecological Research     Open Access  
Visegrad Journal on Bioeconomy and Sustainable Development     Open Access   (Followers: 1)
Zeitschrift für Naturforschung B : A Journal of Chemical Sciences     Open Access   (Followers: 1)


Journal Cover Computational Biology and Chemistry
  [SJR: 0.491]   [H-I: 47]   [9 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 1476-9271
   Published by Elsevier Homepage  [3039 journals]
  • Free radical scavenging and COX-2 inhibition by simple colon metabolites
           of polyphenols: A theoretical approach
    • Abstract: Publication date: Available online 23 September 2016
      Source:Computational Biology and Chemistry
      Author(s): Ana Amić, Zoran Marković, Jasmina M. Dimitrić Marković, Svetlana Jeremić, Bono Lučić, Dragan Amić
      Free radical scavenging and inhibitory potency against cyclooxygenase-2 (COX-2) by two abundant colon metabolites of polyphenols, i.e., 3-hydroxyphenylacetic acid (3-HPAA) and 4-hydroxyphenylpropionic acid (4-HPPA) were theoretically studied. Different free radical scavenging mechanisms are investigated in water and pentyl ethanoate as a solvent. By considering electronic properties of scavenged free radicals, hydrogen atom transfer (HAT) and sequential proton loss electron transfer (SPLET) mechanisms are found to be thermodynamically probable and competitive processes in both media. The Gibbs free energy change for reaction of inactivation of free radicals indicates 3-HPAA and 4-HPPA as potent scavengers. Their reactivity toward free radicals was predicted to decrease as follows: hydroxyl>>alkoxyls>phenoxyl≈peroxyls>>superoxide. Shown free radical scavenging potency of 3-HPAA and 4-HPPA along with their high μM concentration produced by microbial colon degradation of polyphenols could enable at least in situ inactivation of free radicals. Docking analysis with structural forms of 3-HPAA and 4-HPPA indicates dianionic ligands as potent inhibitors of COX-2, an inducible enzyme involved in colon carcinogenesis. Obtained results suggest that suppressing levels of free radicals and COX-2 could be achieved by 3-HPAA and 4-HPPA indicating that these compounds may contribute to reduced risk of colon cancer development.
      Graphical abstract image

      PubDate: 2016-09-27T17:47:48Z
  • 1,3-oxazole derivatives as potential anticancer agents: computer modeling
           and experimental study
    • Abstract: Publication date: Available online 21 September 2016
      Source:Computational Biology and Chemistry
      Author(s): Ivan Semenyuta, Vasyl Kovalishyn, Vsevolod Tanchuk, Stepan Pilyo, Vladimir Zyabrev, Volodymyr Blagodatnyy, Olena Trokhimenko, Volodymyr Brovarets, Larysa Metelytsia
      Microtubules play a significant role in cell growth and functioning. Therefore inhibition of the microtubule assemblies has emerged as one of the most promising cancer treatment strategies. Predictive QSAR models were built on a series of selective inhibitors of the tubulin were performed by using Associative Neural Networks (ANN). To overcome the problem of data overfitting due to the descriptor selection, a 5-fold cross-validation with variable selection in each step of the analysis was used. All developed QSAR models showed excellent statistics on the training (total accuracy: 0.96–0.97) and test sets (total accuracy: 0.95–97). The models were further validated by 11 synthesized 1,3-oxazole derivatives and all of them showed inhibitory effect on the Hep-2 cancer cell line. The most promising compound showed inhibitory activity IC50 =60.2 μM. In order to hypothesize their mechanism of action the top three compounds were docked in the colchicine binding site of tubulin and showed reasonable docking scores as well as favorable interactions with the protein.
      Graphical abstract image

      PubDate: 2016-09-23T04:35:10Z
  • Comparison among dimensionality reduction techniques based on Random
           Projection for cancer classification
    • Abstract: Publication date: Available online 21 September 2016
      Source:Computational Biology and Chemistry
      Author(s): Haozhe Xie, Jie Li, Qiaosheng Zhang, Yadong Wang
      Random Projection (RP) technique has been widely applied in many scenarios because it can reduce high-dimensional features into low-dimensional space within short time and meet the need of real-time analysis of massive data. There is an urgent need of dimensionality reduction with fast increase of big genomics data. However, the performance of RP is usually lower. We attempt to improve classification accuracy of RP through combining other reduction dimension methods such as Principle Component Analysis (PCA), Linear Discriminant Analysis (LDA), and Feature Selection (FS). We compared classification accuracy and running time of different combination methods on three microarray datasets and a simulation dataset. Experimental results show a remarkable improvement of 14.77% in classification accuracy of FS followed by RP compared to RP on BC-TCGA dataset. LDA followed by RP also helps RP to yield a more discriminative subspace with an increase of 13.65% on classification accuracy on the same dataset. FS followed by RP outperforms other combination methods in classification accuracy on most of the datasets.

      PubDate: 2016-09-23T04:35:10Z
  • Predicting protein subcellular localization based on information content
           of gene ontology terms
    • Abstract: Publication date: Available online 14 September 2016
      Source:Computational Biology and Chemistry
      Author(s): Shu-Bo Zhang, Qiang-Rong Tang
      Predicting the location where a protein resides within a cell is important in cell biology. Computational approaches to this issue have attracted more and more attentions from the community of biomedicine. Among the protein features used to predict the subcellular localization of proteins, the feature derived from Gene Ontology (GO) has been shown to be superior to others. However, most of the sights in this field are set on the presence or absence of some predefined GO terms. We proposed a method to derive information from the intrinsic structure of the GO graph. The feature vector was constructed with each element in it representing the information content of the GO term annotating to a protein investigated, and the support vector machines was used as classifier to test our extracted features. Evaluation experiments were conducted on three protein datasets and the results show that our method can enhance eukaryotic and human subcellular location prediction accuracy by up to 1.1% better than previous studies that also used GO-based features. Especially in the scenario where the cellular component annotation is absent, our method can achieved satisfied results with an overall accuracy of more than 87%.
      Graphical abstract image

      PubDate: 2016-09-19T04:30:37Z
  • NoisyGOA: noisy GO annotations prediction using taxonomic and semantic
    • Abstract: Publication date: Available online 9 September 2016
      Source:Computational Biology and Chemistry
      Author(s): Chang Lu, Jun Wang, Zili Zhang, Pengyi Yang, Guoxian Yu
      Gene Ontology (GO) provides GO annotations (GOA) that associate gene products with GO terms that summarize their cellular, molecular and functional aspects in the context of biological pathways. GO Consortium (GOC) resorts to various quality assurances to ensure the correctness of annotations. Due to resources limitations, only a small portion of annotations are manually added/checked by GO curators, and a large portion of available annotations are computationally inferred. While computationally inferred annotations provide greater coverage of known genes, they may also introduce annotation errors (noise) that could mislead the interpretation of the gene functions and their roles in cellular and biological processes. In this paper, we investigate how to identify noisy annotations, a rarely addressed problem, and propose a novel approach called NoisyGOA. NoisyGOA first measures taxonomic similarity between ontological terms using the GO hierarchy and semantic similarity between genes. Next, it leverages the taxonomic similarity and semantic similarity to predict noisy annotations. We compare NoisyGOA with other alternative methods on identifying noisy annotations under different simulated cases of noisy annotations, and on archived GO annotations. NoisyGOA achieved higher accuracy than other alternative methods in comparison. These results demonstrated both taxonomic similarity and semantic similarity contribute to the identification of noisy annotations. Our study shows that annotation errors are predictable and removing noisy annotations improves the performance of gene function prediction. This study can prompt the community to study methods for removing inaccurate annotations, a critical step for annotating gene and pathway functions. Matlab codes of NoisyGOA are available at

      PubDate: 2016-09-14T04:11:47Z
  • Structure-based design and evaluation of novel N-phenyl-1H-indol-2-amine
           derivatives for fat mass and obesity-associated (FTO) protein inhibition
    • Abstract: Publication date: Available online 9 September 2016
      Source:Computational Biology and Chemistry
      Author(s): Monikaben Padariya, Umesh Kalathiya
      Fat mass and obesity-associated (FTO) protein contributes to non-syndromic human obesity which refers to excessive fat accumulation in human body and results in health risk. FTO protein has become a promising target for anti-obesity medicines as there is an immense need for the rational design of potent inhibitors to treat obesity. In our study, a new scaffold N-phenyl-1H-indol-2-amine was selected as a base for FTO protein inhibitors by applying scaffold hopping approach. Using this novel scaffold, different derivatives were designed by extending scaffold structure with potential functional groups. Molecular docking simulations were carried out by using two different docking algorithm implemented in CDOCKER (flexible docking) and AutoDock programs (rigid docking). Analyzing results of rigid and flexible docking, compound MU06 was selected based on different properties and predicted binding affinities for further analysis. Molecular dynamics simulation of FTO/MU06 complex was performed to characterize structure rationale and binding stability. Certainly, Arg96 and His231 residue of FTO protein showed stable interaction with inhibitor MU06 throughout the production dynamics phase. Three residues of FTO protein (Arg96, Asp233, and His231) were found common in making H-bond interactions with MU06 during molecular dynamics simulation and CDOCKER docking.
      Graphical abstract image

      PubDate: 2016-09-14T04:11:47Z
  • NSAMD: A new approach to discover structured contiguous substrings in
           sequence datasets using Next-Symbol-Array
    • Abstract: Publication date: October 2016
      Source:Computational Biology and Chemistry, Volume 64
      Author(s): Abdolvahed Pari, Ahmad Baraani, Saeed Parseh
      In many sequence data mining applications, the goal is to find frequent substrings. Some of these applications like extracting motifs in protein and DNA sequences are looking for frequently occurring approximate contiguous substrings called simple motifs. By approximate we mean that some mismatches are allowed during similarity test between substrings, and it helps to discover unknown patterns. Structured motifs in DNA sequences are frequent structured contiguous substrings which contains two or more simple motifs. There are some works that have been done to find simple motifs but these works have problems such as low scalability, high execution time, no guarantee to find all patterns, and low flexibility in adaptation to other application. The Flame is the only algorithm that can find all unknown structured patterns in a dataset and has solved most of these problems but its scalability for very large sequences is still weak. In this research a new approach named Next-Symbol-Array based Motif Discovery (NSAMD) is represented to improve scalability in extracting all unknown simple and structured patterns. To reach this goal a new data structure has been presented called Next-Symbol-Array. This data structure makes change in how to find patterns by NSAMD in comparison with Flame and helps to find structured motif faster. Proposed algorithm is as accurate as Flame and extracts all existing patterns in dataset. Performance comparisons show that NSAMD outperforms Flame in extracting structured motifs in both execution time (51% faster) and memory usage (more than 99%). Proposed algorithm is slower in extracting simple motifs but considerable improvement in memory usage (more than 99%) makes NSAMD more scalable than Flame. This advantage of NSAMD is very important in biological applications in which very large sequences are applied.
      Graphical abstract image

      PubDate: 2016-09-09T19:47:22Z
  • BS-RNA: an efficient mapping and annotation tool for RNA bisulfite
           sequencing data
    • Abstract: Publication date: Available online 9 September 2016
      Source:Computational Biology and Chemistry
      Author(s): Fang Liang, Lili Hao, Jinyue Wang, Shuo Shi, Jingfa Xiao, Rujiao Li
      Cytosine methylation is one of the most important RNA epigenetic modifications. With the development of experimental technology, scientists attach more importance to RNA cytosine methylation and find bisulfite sequencing is an effective experimental method for RNA cytosine methylation study. However, there are only a few tools can directly deal with RNA bisulfite sequencing data efficiently. Herein, we developed a specialized tool BS-RNA, which can analyze cytosine methylation of RNA based on bisulfite sequencing data and support both paired-end and single-end sequencing reads from directional bisulfite libraries. For paired-end reads, simply removing the biased positions from the 5′ end may result in “dovetailing” reads, where one or both reads seem to extend past the start of the mate read. BS-RNA could map “dovetailing” reads successfully. The annotation result of BS-RNA is exported in BED (.bed) format, including locations, sequence context types (CG/CHG/CHH, H=A,T, or C), reference sequencing depths, cytosine sequencing depths, and methylation levels of covered cytosine sites on both Watson and Crick strands. BS-RNA is an efficient, specialized and highly automated mapping and annotation tool for RNA bisulfite sequencing data. It performs better than the existing program in terms of accuracy and efficiency. BS-RNA is developed by Perl language and the source code of this tool is freely available from the website:

      PubDate: 2016-09-09T19:47:22Z
  • Assessing the similarity of ligand binding conformations with the Contact
           Mode Score
    • Abstract: Publication date: Available online 6 September 2016
      Source:Computational Biology and Chemistry
      Author(s): Yun Ding, Ye Fang, Juana Moreno, J. Ramanujam, Mark Jarrell, Michal Brylinski
      Structural and computational biologists often need to measure the similarity of ligand binding conformations. The commonly used root-mean-square deviation (RMSD) is not only ligand-size dependent, but also may fail to capture biologically meaningful binding features. To address these issues, we developed the Contact Mode Score (CMS), a new metric to assess the conformational similarity based on intermolecular protein-ligand contacts. The CMS is less dependent on the ligand size and has the ability to include flexible receptors. In order to effectively compare binding poses of non-identical ligands bound to different proteins, we further developed the eXtended Contact Mode Score (XCMS). We believe that CMS and XCMS provide a meaningful assessment of the similarity of ligand binding conformations. CMS and XCMS are freely available at and
      Graphical abstract image

      PubDate: 2016-09-09T19:47:22Z
  • The interactome of CCT Complex- A computational analysis
    • Abstract: Publication date: Available online 6 September 2016
      Source:Computational Biology and Chemistry
      Author(s): N. Aswathy, Dileep Pullepu, MAnaul Kabir
      The eukaryotic chaperonin, CCT (Chaperonin Containing TCP1 or TriC-TCP-1 Ring Complex) has been subjected to physical and genetic analyses in S.cerevisiae which can be extrapolated to human CCT (hCCT), owing to its structural and functional similarities with yeast CCT (yCCT). Studies on hCCT and its interactome acquire an additional dimension, as it has been implicated in several disease conditions like neurodegeneration and cancer. We attempt to study its stress response role in general, which will be reflected in the aspects of human diseases and yeast physiology, through computational analysis of the interactome. Towards consolidating and analysing the interactome data, we prepared and compared the unique CCT-interacting protein lists for S.cerevisiae and H.sapiens, performed GO term classification and enrichment studies which provide information on the diversity in CCT interactome, in terms of protein classes in the data set. Enrichment with disease-associated proteins and pathways highlight the medical importance of CCT. Different analyses converge, suggesting the significance of WD-repeat proteins, protein kinases and cytoskeletal proteins in the interactome. The prevalence of proteasomal subunits and ribosomal proteins suggest a possible cross-talk between protein-synthesis, folding and degradation machinery. A network of chaperones and chaperonins that function in combination can also be envisaged from the CCT interactome-Hsp70 interactome analysis.
      Graphical abstract image

      PubDate: 2016-09-09T19:47:22Z
  • SnpFilt: A pipeline for reference-free assembly-based identification of
           SNPs in bacterial genomes
    • Abstract: Publication date: Available online 9 September 2016
      Source:Computational Biology and Chemistry
      Author(s): Carmen H.S. Chan, Sophie Octavia, Vitali Sintchenko, Ruiting Lan
      De novo assembly of bacterial genomes from next-generation sequencing (NGS) data allows a reference-free discovery of single nucleotide polymorphisms (SNP). However, substantial rates of errors in genomes assembled by this approach remain a major barrier for the reference-free analysis of genome variations in medically important bacteria. The aim of this report was to improve the quality of SNP identification in bacterial genomes without closely related references. We developed a bioinformatics pipeline (SnpFilt) that constructs an assembly using SPAdes and then removes unreliable regions based on the quality and coverage of re-aligned reads at neighbouring regions. The performance of the pipeline was compared against reference-based SNP calling for Illumina HiSeq, MiSeq and NextSeq reads from a range of bacterial pathogens including Salmonella, which is one of the most common causes of food-borne disease. The SnpFilt pipeline removed all false SNP in all test NGS datasets consisting of paired-end Illumina reads. We also showed that for reliable and complete SNP calls, at least 40-fold coverage is required. Analysis of bacterial isolates associated with epidemiologically confirmed outbreaks using the SnpFilt pipeline produced results consistent with previously published findings. The SnpFilt pipeline improves the quality of de-novo assembly and precision of SNP calling in bacterial genomes by removal of regions of the assembly that may potentially contain assembly errors. SnpFilt is available from
      Graphical abstract image

      PubDate: 2016-09-09T19:47:22Z
  • Marine derived compounds as binders of the White spot syndrome virus VP28
           envelope protein: In silico insights from molecular dynamics and binding
           free energy calculations
    • Abstract: Publication date: Available online 28 August 2016
      Source:Computational Biology and Chemistry
      Author(s): K.C. Sivakumar, T.P. Sajeevan, I.S. Bright Singh
      White spot syndrome virus (WSSV) remains as one of the most dreadful pathogen of the shrimp aquaculture industry owing to its high virulence. The cumulative mortality reaches up to 100% within in 2–10days in a shrimp farm. Currently, no chemotherapeutics are available to control WSSV. The viral envelope protein, VP28, located on the surface of the virus particle acts as a vital virulence factor in the initial phases of inherent WSSV infection in shrimp. Hence, inhibition of envelope protein VP28 could be a novel way to deal with infection by inhibiting its interaction in the endocytic pathway. In this direction, a timely attempt was made to recognize a potential drug candidate of marine origin against WSSV using VP28 as a target by employing in silico docking and molecular dynamic simulations. A virtual library of 388 marine bioactive compounds was extracted from reports published in Marine Drugs. The top ranking compounds from docking studies were chosen from the flexible docking based on the binding affinities (ΔGb). In addition, the MD simulation and binding free energy analysis were implemented to validate and capture intermolecular interactions. The results suggested that the two compounds obtained a negative binding free energy with −40.453kJ/mol and −31.031kJ/mol for compounds with IDs 30797199 and 144162 respectively. The RMSD curve indicated that 30797199 moves into the hydrophobic core, while the position of 144162 atoms changes abruptly during simulation and is mostly stabilized by water bridges. The shift in RMSD values of VP28 corresponding to ligand RMSD gives an insight into the ligand induced conformational changes in the protein. This study is first of its kind to elucidate the explicit binding of chemical inhibitor to WSSV major structural protein VP28.
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      PubDate: 2016-08-31T19:28:06Z
  • Identification and characterization of promoters and cis-regulatory
           elements of genes involved in secondary metabolites production in hop
           (Humulus lupulus. L)
    • Abstract: Publication date: Available online 24 August 2016
      Source:Computational Biology and Chemistry
      Author(s): Ganesh Selvaraj Duraisamy, Ajay Kumar Mishra, Tomas Kocabek, Jaroslav Matoušek
      Molecular and biochemical studies have shown that gene contains single or combination of different cis-acting regulatory elements are actively controlling the transcriptional regulation of associated genes, downstream effects of these result in modulation of various biological pathways such as biotic/abiotic stress responses, hormonal responses to growth and development processes and secondary metabolite production. Therefore, the identification of promoters and their cis-regulatory elements is one of intriguing area to study the dynamic complex regulatory network of genes activities by integrating computational, comparative, structural and functional genomics. A variety of bioinformatics servers or database have been established to predict the cis-acting elements present in the promoter region of target gene and their association with the expression profiles in the TFs. The aim of this study is to predict possible cis-acting regulatory elements that have putative role in the transcriptional regulation of a dynamic network of metabolite gene activities controlling prenylflavonoid and bitter acids biosynthesis in hop (Humulus lupulus). Recent release of hop draft genome enabled us to predict the possible cis-acting regulatory elements by extracting 2kbp of 5′ regulatory regions of genes important for lupulin metabolome biosynthesis, using Plant CARE, PLACE and Genomatix Matinspector professional databases. The result reveals the plausible role of cis-acting regulatory elements in the regulation of gene expression primarily involved in lupulin metabolome biosynthesis including under various stress conditions.
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      PubDate: 2016-08-27T19:11:14Z
  • Hybrid docking-QSAR studies of DPP-IV inhibition activities of a series of
    • Abstract: Publication date: Available online 20 August 2016
      Source:Computational Biology and Chemistry
      Author(s): Zohreh Amini, Mohammad Hossein Fatemi, Sajjad Gharaghani
      In this study, the dipeptidyl peptidase-IV (DPP-IV) inhibition activities of a series of novel aminomethyl-piperidones were investigated by molecular docking studies and modeled by quantitative structure–activity relationship (QSAR) methodology. Molecular docking studies were used to find the best conformations of the studied molecules in the active site of DPP-IV protein. Then the best docking-derived conformation for each molecule was applied for calculating the molecular descriptors. Multiple linear regression (MLR) and Levenberg–Marquardt artificial neural network (LM-ANN) were conducted on descriptors derived by docking. The results of these models revealed the superiority of LM-ANN model over MLR which showed the nonlinear relationship between the selected molecular descriptors and DPP-IV inhibition activities of studied molecules. The correlation coefficient (R) and standard error (SE) of ANN model were 0.983 and 0.103 for the training set and 0.966 and 0.168 for the external test set. These results showed a close agreement between the experimental and calculated values of pIC50 which demonstrated the robustness of LM-ANN model in modeling of aminomethyl-piperidones. Applicability domain analysis and sensitivity analysis were applied on the obtained models. This study gives useful information for further experimental studies on DPP-IV inhibitors. The results of this work reveal the applicability of hybrid docking-QSAR methodology in ligand-protein studies.
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      PubDate: 2016-08-23T19:01:12Z
  • Inhibitory activity of hibifolin on adenosine deaminase- experimental and
           molecular modeling study
    • Abstract: Publication date: Available online 22 August 2016
      Source:Computational Biology and Chemistry
      Author(s): K.G. Arun, C.S. Sharanya, P.M. Sandeep, C. Sadasivan
      Adenosine deaminase (ADA) is an enzyme involved in purine metabolism. ADA converts adenosine to inosine and liberates ammonia. Because of their critical role in the differentiation and maturation of cells, the regulation of ADA activity is considered as a potential therapeutic approach to prevent malignant and inflammatory disorders. In the present study, the inhibitory activity of a plant flavonoid, hibifolin on ADA is investigated using enzyme kinetic assay and isothermal titration calorimetry. The inhibitory constant of hibifolin was found to be 49.92μM±3.98 and the mode of binding was reversible. Isothermal titration calorimetry showed that the compound binds ADA with binding energy of −7.21Kcal/mol. The in silico modeling and docking studies showed that the bound ligand is stabilized by hydrogen bonds with active site residues of the enzyme. The study reveals that hibifolin can act as a potential inhibitor of ADA.
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      PubDate: 2016-08-23T19:01:12Z
  • Roles of the respective loops at complementarity determining region on the
           antigen-antibody recognition
    • Abstract: Publication date: Available online 23 August 2016
      Source:Computational Biology and Chemistry
      Author(s): Tomonori Osajima, Tyuji Hoshino
      For the rational design of antibody, it is important to clarify the characteristics of the interaction between antigen and antibody. In this study, we evaluated a contribution of the respective complementarity determining region (CDR) loops on the antibody recognition of antigen by performing molecular dynamics simulations for 20 kinds of antigen-antibody complexes. Ser and Tyr showed high appearance rates at CDR loops and the sum of averaged appearance rates of Ser and Tyr was about 20 − 30% at all the loops. For example, Ser and Tyr occupied 23.9% at the light chain first loop (L1) and 23.6% at the heavy chain third loop (H3). The direct hydrogen bonds between antigen and antibody were not equally distributed over heavy and light chains. That is, about 70% of the hydrogen bonds were observed at CDRs of the heavy chain and also the direct hydrogen bond with the shortest distance mainly existed at the loops of the heavy chain for all the complexes. It was revealed from the comparison in contribution to the binding free energy among CDR loops that the heavy chain (especially at H2 and H3) had significant influence on the binding between antigen and antibody because three CDR loops of the heavy chain showed the lowest binding free energy (ΔG bind) in 19 complexes out of 20. Tyr in heavy chain (especially in H2 and H3) largely contributed to ΔG bind whereas Ser hardly contributed to ΔG bind even if the number of the direct hydrogen bond with Ser was the fourth largest and also the appearance rate at CDR was the highest among 20 kinds of amino acid residues. The contributions ofTrp and Phe, which bear aromatic ring in the side chain, were often observed in the heavy chain although the energetic contribution of these residues was not so high as Tyr. The present computational analysis suggests that Tyr plays an outstanding role for the antigen-antibody interaction and the CDR loops of the heavy chain is critically important for antibody recognition of antigen.
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      PubDate: 2016-08-23T19:01:12Z
  • Recurrent Neural Network Based Hybrid Model for Reconstructing Gene
           Regulatory Network
    • Abstract: Publication date: Available online 16 August 2016
      Source:Computational Biology and Chemistry
      Author(s): Khalid Raza, Mansaf Alam
      One of the exciting problems in systems biology research is to decipher how genome controls the development of complex biological system. The gene regulatory networks (GRNs) help in the identification of regulatory interactions between genes and offer fruitful information related to functional role of individual gene in a cellular system. Discovering GRNs lead to a wide range of applications, including identification of disease related pathways providing novel tentative drug targets, helps to predict disease response, and also assists in diagnosing various diseases including cancer. Reconstruction of GRNs from available biological data is still an open problem. This paper proposes a recurrent neural network (RNN) based model of GRN, hybridized with generalized extended Kalman filter for weight update in backpropagation through time training algorithm. The RNN is a complex neural network that gives a better settlement between biological closeness and mathematical flexibility to model GRN; and is also able to capture complex, non-linear and dynamic relationships among variables. Gene expression data are inherently noisy and Kalman filter performs well for estimation problem even in noisy data. Hence, we applied non-linear version of Kalman filter, known as generalized extended Kalman filter, for weight update during RNN training. The developed model has been tested on four benchmark networks such as DNA SOS repair network, IRMA network, and two synthetic networks from DREAM Challenge. We performed a comparison of our results with other state-of-the-art techniques which shows superiority of our proposed model. Further, 5% Gaussian noise has been induced in the dataset and result of the proposed model shows negligible effect of noise on results, demonstrating the noise tolerance capability of the model.
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      PubDate: 2016-08-18T18:52:00Z
  • Structural insight into the glucokinase-ligands interactions. Molecular
           docking study
    • Abstract: Publication date: Available online 8 August 2016
      Source:Computational Biology and Chemistry
      Author(s): Elena Ermakova
      Glucokinase (GK) plays a key role in the regulation of hepatic glucose metabolism. Inactivation of GK is associated with diabetes, and an increase of its activity is linked to hypoglycemia. Possibility to regulate the GK activity using small chemical compounds as allosteric activators induces the scientific interest to the study of the activation mechanism and to the development of new allosteric glucokinase activators. Interaction of glucokinase with ligands is the first step of the complicated mechanism of regulation of the GK functioning. In this paper, we study the interaction of GK with native (glucose) and synthetic (allosteric activators) ligands using molecular docking method. Calculations demonstrate the ability of molecular docking programs to accurately reproduce crystallized ligand poses and conformations and to calculate a free energy of binding with satisfactory accuracy. Correlation between the free energy of binding and the bioactivity of activators is discussed. These results provide a new insight into protein–ligand interactions and can be used for the engineering of new activators.
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      PubDate: 2016-08-11T12:45:08Z
  • Steric exclusion and constraint satisfaction in multi-scale coarse-grained
    • Abstract: Publication date: Available online 6 August 2016
      Source:Computational Biology and Chemistry
      Author(s): William R. Taylor
      An algorithm is described for the interaction of a hierarchy of objects that seeks to circumvent a fundamental problem in coarse-grained modelling which is the loss of fine detail when components become bundled together. A “currants-in-jelly” model is developed that provides a flexible approach in which the contribution of the soft high-level objects (jelly-like) are employed to protect the underlying atomic structure (currants), while still allowing them to interact. Idealised chains were used to establish the parameters to achieve this degree of interaction over a hierarchy spanning four levels and in a more realistic example, the distortion experienced by a protein domain structure during collision was measured and the parameters refined. This model of steric repulsion was then combined with sets of predicted distance constraints, derived from correlated mutation analysis. Firstly, an integral trans-membrane protein was modelled in which the packing of the seven helices was refined but without topological rearrangement. Secondly, an RNA structure was ‘folded’ under the predicted constraints, starting only from its 2-dimensional secondary structure prediction.
      Graphical abstract image Highlights

      PubDate: 2016-08-11T12:45:08Z
  • IFC Editorial Board
    • Abstract: Publication date: August 2016
      Source:Computational Biology and Chemistry, Volume 63

      PubDate: 2016-08-07T02:45:57Z
  • Title page
    • Abstract: Publication date: August 2016
      Source:Computational Biology and Chemistry, Volume 63

      PubDate: 2016-08-07T02:45:57Z
  • Assembly of ligands interaction models for glutathione-S-transferases from
           Plasmodium falciparum, human and mouse using enzyme kinetics and molecular
    • Abstract: Publication date: Available online 25 July 2016
      Source:Computational Biology and Chemistry
      Author(s): Mohammed Nooraldeen Al-Qattan, Mohd Nizam Mordi, Sharif Mahsofi Mansor
      Background Glutathione-s-transferases (GSTs) are enzymes that principally catalyze the conjugation of electrophilic compounds to the endogenous nucleophilic glutathione substrate, besides, they have other non-catalytic functions. The Plasmodium falciparum genome encodes a single isoform of GST (PfGST) which is involved in buffering the toxic heme, thus considered a potential anti-malarial target. In mammals several classes of GSTs are available, each of various isoforms. The human (human GST Pi-1 or hGSTP1) and mouse (murine GST Mu-1 or mGSTM1) GST isoforms control cellular apoptosis by interaction with signaling proteins, thus considered as potential anti-cancer targets. In the course of GSTs inhibitors development, the models of ligands interactions with GSTs are used to guide rational molecular modification. In the absence of X-ray crystallographic data, enzyme kinetics and molecular docking experiments can aid in addressing ligands binding modes to the enzymes. Methods Kinetic studies were used to investigate the interactions between the three GSTs and each of glutathione, 1-chloro-2,4-dinitrobenzene, cibacron blue, ethacrynic acid, S-hexyl glutathione, hemin and protoporphyrin IX. Since hemin displacement is intended for PfGST inhibitors, the interactions between hemin and other ligands at PfGST binding sites were studied kinetically. Computationally determined binding modes and energies were interlinked with the kinetic results to resolve enzymes-ligands interaction models at atomic level. Results The results showed that hemin and cibacron blue have different binding modes in the three GSTs. Hemin has two binding sites (A and B) with two binding modes at site-A depending on presence of GSH. None of the ligands were able to compete hemin binding to PfGST except ethacrynic acid. Besides bind differently in GSTs, the isolated anthraquinone moiety of cibacron blue is not maintaining sufficient interactions with GSTs to be used as a lead. Similarly, the ethacrynic acid uses water bridges to mediate interactions with GSTs and at least the conjugated form of EA is the true hemin inhibitor, thus EA may not be a suitable lead. Conclusions Glutathione analogues with bulky substitution at thiol of cysteine moiety or at γ-amino group of γ-glutamine moiety may be the most suitable to provide GST inhibitors with hemin competition.

      PubDate: 2016-07-28T18:33:42Z
  • Evolution of camel CYP2E1 and its associated power of binding toxic
           industrial chemicals and drugs
    • Abstract: Publication date: Available online 26 July 2016
      Source:Computational Biology and Chemistry
      Author(s): Mahmoud Kandeel, Abdullah Altaher, Yukio Kitade, Magdi Abdelaziz, Mohamed Alnazawi, Kamal Elshazli
      Camels are raised in harsh desert environment for hundreds of years ago. By modernization of live and the growing industrial revolution in camels rearing areas, camels are exposed to considerable amount of chemicals, industrial waste, environmental pollutions and drugs. Furthermore, camels have unique gene evolution of some genes to withstand living in harsh environments. In this work, the camel cytochrome P450 2E1 (CYP2E1) is compromised to detect its evolution rate and its power to bind with various chemicals, protoxins, procarcinogens, industrial toxins and drugs. In comparison with human CYP2E1, camel CYP2E1 more efficiently binds to small toxins as aniline, benzene, catechol, amides, butadiene, toluene and acrylamide. Larger compounds were more preferentially bound to the human CYP2E1 in comparison with camel CYP2E1. The binding of inhalant anesthetics was almost similar in both camel and human CYP2E1 coinciding with similar anesthetic effect as well as toxicity profiles. Furthermore, evolutionary analysis indicated the high evolution rate of camel CYP2E1 in comparison with human, farm and companion animals. The evolution rate of camel CYP2E1 was among the highest evolution rate in a subset of 57 different organisms. These results indicate rapid evolution and potent toxin binding power of camel CYP2E1.
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      PubDate: 2016-07-28T18:33:42Z
  • Functional and Structural Insights into Novel DREB1A Transcription Factors
           in Common Wheat (Triticum aestivum L.): A Molecular Modeling Approach
    • Abstract: Publication date: Available online 19 July 2016
      Source:Computational Biology and Chemistry
      Author(s): Anuj Kumar, Sanjay Kumar, Upendra Kumar, Prashanth Suravajhala, M.N.V. Prasad Gajula
      Triticum aestivum L. known as common wheat is one of the most important cereal crops feeding a large and growing population. Various environmental stress factors including drought, high salinity and heat etc. adversely affect wheat production in a significant manner. Dehydration-responsive element-binding (DREB1A) factors, a class of transcription factors (TF) play an important role in combating drought stress. It is known that DREB1A specifically interacts with the dehydration responsive elements (DRE/CRT) inducing expression of genes involved in environmental stress tolerance in plants. Despite its critical interplay in plants, the structural and functional aspects of DREB1A TF in wheat remain unresolved. Previous studies showed that wheat DREBs (DREB1 and DREB2) were isolated using various methods including yeast two-hybrid screens but no extensive structural models were reported. In this study, we made an extensive in silico study to gain insight into DREB1A TF and reported the location of novel DREB1A in wheat chromosomes. We inferred the three-dimensional structural model of DREB1A using homology modelling and further evaluated them using molecular dynamics(MD) simulations yielding refined modelled structures. Our biochemical function predictions suggested that the wheat DREB1A orthologs have similar biochemical functions and pathways to that of AtDREB1A. In conclusion, the current study presents a structural perspective of wheat DREB1A and helps in understanding the molecular basis for the mechanism of DREB1A in response to environmental stress.

      PubDate: 2016-07-24T18:28:20Z
  • In-silico structural analysis of E509K mutation in LARGE and T192M
           mutation in Alpha Dystroglycan in the inhibition of glycosylation of Alpha
           Dystroglycan by LARGE
    • Abstract: Publication date: Available online 16 July 2016
      Source:Computational Biology and Chemistry
      Author(s): Simanti Bhattacharya, Amit Das, Angshuman Bagchi
      Impaired glycosylation of cellular receptor Alpha Dystroglycan (α-DG) leads to dystroglycanopathy. Glycoprotein α-DG is the receptor protein in the Dystrophin Associated Protein Complex (DAPC), a macromolecular gathering on muscle cell membrane to form a bridge between extracellular matrix (ECM) and cellular actin cytoskeleton. Proper glycosylation of α-DG is mediated by the glycosylating enzyme LARGE. Mutations either in α-DG or in LARGE lead to improper glycosylations of α-DG thereby hampering the formation of final Laminin binding form α-DG resulting in dystroglycanopathy. In our current work, we explored the structural changes associated with the presence of mutations in α-DG as well as in the enzyme LARGE. We further extended our research to understand the effect of the mutations onto protein-enzyme interactions. Moreover, since LARGE transfers the sugar moiety (glucuronic acid; GlcA) onto α-DG, we tried to analyze what effect the mutation in LARGE confers on this enzyme ligand interaction. This work for the first time addressed the molecular changes occurring in the structures α-DG, LARGE and their interactions and shed lights on the as yet poorly understood mechanism behind the dystroglycanopathy onset.
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      PubDate: 2016-07-19T18:23:15Z
  • An integrative approach predicted co-expression sub-networks regulating
           properties of stem cells and differentiation
    • Abstract: Publication date: Available online 18 July 2016
      Source:Computational Biology and Chemistry
      Author(s): Mousumi Sahu, Bibekanand Mallick
      The differentiation of human Embryonic Stem Cells (hESCs) is accompanied by the formation of different intermediary cells, gradually losing its stemness and acquiring differentiation. The precise mechanisms underlying hESCs integrity and its differentiation into fibroblast (Fib) are still elusive. Here, we aimed to assess important genes and co-expression sub-networks responsible for stemness, early differentiation of hESCs into embryoid bodies (EBs) and its lineage specification into Fibs. To achieve this, we compared transcriptional profiles of hESCs-EBs and EBs-Fibs and obtained differentially expressed genes (DEGs) exclusive to hESCs-EBs (early differentiation), EBs-Fibs (late differentiation) and common DEGs in hESCs-EBs and EBs-Fibs. Then, we performed gene set enrichment analysis (GSEA) followed by overrepresentation study and identified key genes for each gene category. The regulations of these genes were studied by integrating ChIP-Seq data of core transcription factors (TFs) and histone methylation marks in hESCs. Finally, we identified co-expression sub-networks from key genes of each gene category using k-clique sub-network extraction method. Our study predicted seven genes edicting core stemness properties forming a co-expression network. From the pathway analysis of sub-networks of hESCs-EBs, we hypothesize that FGF2 is contributing to pluripotent transcription network of hESCs in association with DNMT3B and JARID2 thereby facilitating cell proliferation. On the contrary, FGF2 is found to promote cell migration in Fibs along with DDR2, CAV1, DAB2, and PARVA. Moreover, our study identified three k-clique sub-networks regulating TGF-β signaling pathway thereby promoting EBs to Fibs differentiation by: (i) modulating extracellular matrix involving ITGB1, TGFB1I1 and GBP1, (ii) regulating cell cycle remodeling involving CDKN1A, JUNB and DUSP1 and (iii) helping in epithelial to mesenchymal transition (EMT) involving THBS1, INHBA and LOX. This study put forward the unexplored genes and co-expression sub-networks regulating stemness and different stages of differentiation of hESCs which will undoubtedly add to the comprehensive understanding of hESCs biology.
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      PubDate: 2016-07-19T18:23:15Z
  • Perceptron Ensemble of Graph-based Positive-Unlabeled Learning for Disease
           Gene Identification
    • Abstract: Publication date: Available online 12 July 2016
      Source:Computational Biology and Chemistry
      Author(s): Gholam-Hossein Jowkar, Eghbal G. Mansoori
      Identification of disease genes, using computational methods, is an important issue in biomedical and bioinformatics research. According to observations that diseases with the same or similar phenotype have the same biological characteristics, researchers have tried to identify genes by using machine learning tools. In recent attempts, some semi-supervised learning methods, called positive-unlabeled learning, is used for disease gene identification. In this paper, we present a Perceptron ensemble of graph-based positive-unlabeled learning (PEGPUL) on three types of biological attributes: gene ontologies, protein domains and protein-protein interaction networks. In our method, a reliable set of positive and negative genes are extracted using co-training schema. Then, the similarity graph of genes is built using metric learning by concentrating on multi-rank-walk method to perform inference from labeled genes. At last, a Perceptron ensemble is learned from three weighted classifiers: multilevel support vector machine, k-nearest neighbor and decision tree. The main contributions of this paper are: (i) incorporating the statistical properties of gene data through choosing proper metrics, (ii) statistical evaluation of biological features, and (iii) noise robustness characteristic of PEGPUL via using multilevel schema. In order to assess PEGPUL, we have applied it on 12950 disease genes with 949 positive genes from six class of diseases and 12001 unlabeled genes. Compared with some popular disease gene identification methods, the experimental results show that PEGPUL has reasonable performance.
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      PubDate: 2016-07-15T18:13:11Z
  • The binding mode of picrotoxinin in GABAA-ρ receptors: Insight into the
           subunit’s selectivity in the transmembrane domain
    • Abstract: Publication date: Available online 7 July 2016
      Source:Computational Biology and Chemistry
      Author(s): Moawiah M. Naffaa, Abdul Samad
      The channel blocker picrotoxinin has been studied with GABAA-ρ1 and GABAA-ρ2 homology models based on the GluCl crystal structure. Picrotoxinin is tenfold more potent for GABAA-ρ2 than for GABAA-ρ1 homomeric channels. This intra-subunit selectivity arises from the unconserved residues at the 2′ sites, which are the essential molecular basis for both the binding and potency of picrotoxinin. The serine residues at the 2′ positions of the ρ2 channel are predicted to form multiple hydrogen bonds and hydrophobic interactions with picrotoxinin, whereas the proline residues in the 2′ positions of ρ1 channels are predicted to form only hydrophobic contacts with picrotoxinin. However, although the studied ρ1 P2′G, A, and V models form no hydrogen bonds with picrotoxinin, they may participate in several hydrophobic interactions, and the ligand may have distinctive binding modes with GABAA-ρ mutant channels. Picrotoxinin has a lower Emodel value with ρ2 than ρ1 homomeric models (−47Kcal/mol and −36Kcal/mol, respectively), suggesting that picrotoxin blocks the pores of the ρ2 channels more effectively.
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      PubDate: 2016-07-11T17:59:25Z
  • Synthesis, spectroscopic and computational studies of
           2-(thiophen-2-yl)-2,3-dihydro-1H-perimidine: An enzymes inhibition study
    • Abstract: Publication date: Available online 24 June 2016
      Source:Computational Biology and Chemistry
      Author(s): Mahboob Alam, Dong-Ung Lee
      The biologically relevant molecule; 2-(thiophen-2-yl)-2,3-dihydro-1H-perimidine was synthesized and characterized by FT-IR, UV, 1H and 13C NMR, MS, CHN microanalysis, X-ray crystallography as well as by theoretical, B3LYP/6–311++G(d,p), calculations. The vibrational bands appearing in the FT-IR were assigned with great accuracy using animated modes. Molecular properties like HOMO–LUMO analysis, chemical reactivity descriptors, MEP mapping, dipole moment and natural charges have been presented at the same level of theory. The theoretical results are found in good correlation with the experimental data obtained from the various spectral techniques. Moreover, the Hirshfeld analysis was performed to explore the secondary interactions and associated 2D fingerprint plots. Perimidine molecule displayed promising inhibitory activity against acetylcholinesterase (AChE) as compared to the reference drug, tacrine. Molecular docking was carried out to ascertain the synthesized molecule into the X-ray crystal structures of acetylcholinesterase at the active site to find out the probable binding mode. The results of molecular docking admitted that perimidine may reveal enzyme inhibitor activity.
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      PubDate: 2016-07-07T17:36:17Z
  • Mechanistic insights into mode of action of rice allene oxide synthase on
           hydroxyperoxides: An intermediate step in herbivory-induced jasmonate
    • Abstract: Publication date: Available online 2 July 2016
      Source:Computational Biology and Chemistry
      Author(s): Chetna Tyagi, Archana Singh, Indrakant Kumar Singh
      Various types of oxygenated fatty acids termed ‘oxylipins’ are involved in plant response to herbivory. Oxylipins like jasmonic acid (JA) and green leafy volatiles (GLVs) are formed by the action of enzymes like allene oxide synthase (AOS) and hydroxyperoxide lyase (HPL) respectively. In this study, we focus on AOS of Oryza sativa sb. Japonica, that interact with 9- and 13- hydroxyperoxides to produce intermediates of jasmonate pathway and compare it with rice HPL that yields GLVs. We attempt to elucidate the interaction pattern by computational docking protocols keeping the Arabidopsis AOS system as the reference model system. Both 9-hydroxyperoxide and 13-hydroxyperoxide fit into the active site of AOS completely with Phe347, Phe92, Ile463, Val345, and Asn278 being the common interacting residues. Phe347 and Phe92 were mutated with Leucine and docked again with the hydroxyperoxides. The Phe347→Leu347 mutant showed a different mode of action than AOS-hydroxyperoxide complex with Trp413 in direct bonding with the OOH group of 9-hydroxyperoxide. The loss of Lys88-OOH interaction in 13-hydroxyperoxide and loss-of-interaction of Leu347 indicated the importance of Phe347 residue in hydroxyperoxide catalysis. The second mutant Phe92→Leu92 also shows a very different interaction pattern with 13-hydroxyperoxide but not with 9-hydroxyperoxide.Therefore, it can be concluded that Phe347 is more crucial for AOS functionality than Phe92. The aromatic ring of a Phenylalanine residue is important for catalysis and its mutation affects the binding of the two ligands. Another important residue is Asn278 which is an important part of the AOS catalytic site for maintaining stability and can be compared with the Arabidopsis AOS residue Asn321. Lastly, the interaction of HPL with these two derivatives involves Leu363 residue instead of Phe347 and thus, validating the importance of Phe→Leu substitution to be the reason of different modes of action that result in completely different products from same substrates.
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      PubDate: 2016-07-07T17:36:17Z
  • Revisiting the Structural Basis and Energetic Landscape of Susceptibility
           Difference between HLA Isotypes to Allergic Rhinitis
    • Abstract: Publication date: Available online 6 July 2016
      Source:Computational Biology and Chemistry
      Author(s): Xin-Li Mao, Feng Zhu, Zhao-Hu Pan, Guo-Min Wu, Hong-Yuan Zhu
      The human leukocyte antigen class II (HLA II) molecules are implicated in the immunopathogenesis of allergic rhinitis (AR). The HLA II contains three allelic isotypes HLA-DR, −DQ, and −QP that exhibit considerably different susceptibility to AR. Here, we investigated the structural basis and energetic landscape of the susceptibility difference between the three HLA II isotypes to AR by combining computational analysis and experimental assay. Multiple sequence alignment revealed a low conservation among the three subtypes with sequence identity of ∼10% between them, suggesting that the peptide repertoires presented by HLA-DR, −DP and −DQ are not overlapped to each other, and they may be involved in different immune functions and dysfunctions. Structural analysis imparted that the antigenic peptides are rooted on the peptide-binding groove of HLA molecules and hold in a PPII-like helical conformation. Subsequently, the interaction behavior of 17 AR allergen-derived peptides with HLA-DR, −DP and −DQ was investigated using a statistics-based quantitative structure-activity relationship (QSAR) predictor. It was found a significant difference between the binding capabilities of these antigenic peptides to HLA-DR and to HLA-DP/-DQ; the former showed a generally higher affinity than the latter with p-value of 0.02 obtained from 2-tailed student's t-test. The computational findings were then confirmed by HLA II–peptide stability assay, which demonstrated that the AR allergen-derived peptides have a high in vitro selectivity for HLA-DR over HLA-DP/-DQ. Thus, the HLA-DR isotype, rather than HLA-DP and −DQ, is expected to associate with the pathological process of AR.
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      PubDate: 2016-07-07T17:36:17Z
  • Alphavirus protease inhibitors from natural sources: A homology modeling
           and molecular docking investigation
    • Abstract: Publication date: October 2016
      Source:Computational Biology and Chemistry, Volume 64
      Author(s): Kendall G. Byler, Jasmine T. Collins, Ifedayo Victor Ogungbe, William N. Setzer
      Alphaviruses such as Chikungunya virus (CHIKV), O’Nyong–Nyong virus (ONNV), Ross River virus (RRV), Eastern equine encephalitis virus (EEEV), Venezuelan equine encephalitis virus (VEEV), and Western equine encephalitis virus (WEEV), are mosquito-transmitted viruses that can cause fevers, rash, and rheumatic diseases (CHIKV, ONNV, RRV) or potentially fatal encephalitis (EEEV, VEEV, WEEV) in humans. These diseases are considered neglected tropical diseases for which there are no current antiviral therapies or vaccines available. The alphavirus non-structural protein 2 (nsP2) contains a papain-like protease, which is considered to be a promising target for antiviral drug discovery. In this work, molecular docking analyses have been carried out on a library of 2174 plant-derived natural products (290 alkaloids, 664 terpenoids, 1060 polyphenolics, and 160 miscellaneous phytochemicals) with the nsP2 proteases of CHIKV, ONNV, RRV, EEEV, VEEV, WEEV, as well as Aura virus (AURV), Barmah Forest Virus (BFV), Semliki Forest virus (SFV), and Sindbis virus (SINV) in order to identity structural scaffolds for inhibitor design or discovery. Of the 2174 phytochemicals examined, a total of 127 showed promising docking affinities and poses to one or more of the nsP2 proteases, and this knowledge can be used to guide experimental investigation of potential inhibitors.
      Graphical abstract image

      PubDate: 2016-07-07T17:36:17Z
  • Identification of miRNAs and their targets involved in the secondary
           metabolic pathways of Mentha spp.
    • Abstract: Publication date: Available online 17 June 2016
      Source:Computational Biology and Chemistry
      Author(s): Noopur Singh, Swati Srivastava, Ajit K. Shasany, Ashok Sharma
      The endogenous, small and non-coding functional microRNAs govern the regulatory system of gene expression and control the growth and development of the plants. Mentha spp. are well known herbs for its flavor, fragrance and medicinal properties. In the present study, we used a computational approach to identify miRNAs and their targets involved in different secondary metabolic pathways of Mentha spp. Additionally, phylogenetic and conservation analysis were also done for the predicted miRNAs. Eleven miRNAs families were identified from Mentha spp., out of which five miRNA families were reported for the first time from Lamiaceae. Overall, 130 distinct target transcripts were predicted for eight miRNAs families. All the predicted targets regulated by predicted miRNAs control the reproduction, signaling, stimulus response, developmental and different metabolic process. miRNA mediated gene regulatory network was also constructed on the basis of hybridized minimum free energy of identified miRNAs and their targets. The study revealed that the gene regulatory system of essential oil biosynthesis may be governed by miR156, miR414 and miR5021 in mint family. Furthermore, three miRNA candidates (miR156, miR5021, and miR5015b) were observed to be involved in trichome development also. This is the first in-silico study describing miRNAs and their role in the regulation of secondary metabolic pathways in Mentha spp.
      Graphical abstract image

      PubDate: 2016-06-17T18:10:05Z
  • A model for the clustered distribution of SNPs in the human genome
    • Abstract: Publication date: Available online 8 June 2016
      Source:Computational Biology and Chemistry
      Author(s): Chang-Yong Lee
      Motivated by a non-random but clustered distribution of SNPs, we introduce a phenomenological model to account for the clustering properties of SNPs in the human genome. The phenomenological model is based on a preferential mutation to the closer proximity of existing SNPs. With the Hapmap SNP data, we empirically demonstrate that the preferential model is better for illustrating the clustered distribution of SNPs than the random model. Moreover, the model is applicable not only to autosomes but also to the X chromosome, although the X chromosome has different characteristics from autosomes. The analysis of the estimated parameters in the model can explain the pronounced population structure and the low genetic diversity of the X chromosome. In addition, correlation between the parameters reveals the population-wise difference of the mutation probability. These results support the mutational non-independence hypothesis against random mutation.
      Graphical abstract image Highlights

      PubDate: 2016-06-13T10:05:05Z
  • Comprehensive structural analysis of the open and closed conformations of
           Theileria annulata enolase by molecular modelling and docking
    • Abstract: Publication date: Available online 9 June 2016
      Source:Computational Biology and Chemistry
      Author(s): Ozal Mutlu, Sinem Yakarsonmez, Emrah Sariyer, Ozkan Danis, Basak Yuce-Dursun, Murat Topuzogullari, Ekrem Akbulut, Dilek Turgut-Balik
      Theileria annulata is an apicomplexan parasite which is responsible for tropical theileriosis in cattle. Due to resistance of T. annulata against commonly used antitheilerial drug, new drug candidates should be identified urgently. Enolase might be a druggable protein candidate which has an important role in glycolysis, and could also be related to several cellular functions as a moonlight protein. In this study; we have described three-dimensional models of open and closed conformations of T. annulata enolase by homology modeling method for the first time with the comprehensive domain, active site and docking analyses. Our results show that the enolase has similar folding patterns within enolase superfamily with conserved catalytic loops and active site residues. We have described specific insertions, possible plasminogen binding sites, electrostatic potential surfaces and positively charged pockets as druggable regions in T. annulata enolase.
      Graphical abstract image

      PubDate: 2016-06-13T10:05:05Z
    • Abstract: Publication date: Available online 8 June 2016
      Source:Computational Biology and Chemistry
      Author(s): Arijit Pal, Anusri Tripathi
      Bacterial Oxacillinases (OXAs), genetically being extremely diverse and highly versatile in hydrolyzing antibiotics of different classes, holds utmost significant clinical importance. Hence, to analyze functional evolution of this enzyme, plausible changes in drug profile, affinity and binding stability of different subclasses of OXA with their preferred drugs, viz. penicillin, ceftazidime, imipenem/meropenem were investigated. Maximum-Likelihood dendrogram was constructed and based on tree topology, the least and most divergent variants of each clade were selected. Pocket characterization, enzyme structural stability and mutational effect were analyzed in silico. Modes of interaction of selected OXA variants with respective antibiotics were analyzed by Autodock4.0 and LIGPLOT. Comparative mobility profiling and subsequent ΔG ° and Km calculations of representative OXA variants revealed that after RSBL evolution, perhaps, two competitive strategies evolved among the OXA variants. Either loops flanking helix5 gets stabilized or it becomes more flexible. Therefore, while OXA variants (e.g. OXA-2, OXA-32, OXA-23, OXA-133, OXA-24, OXA-25, OXA-51 and OXA-75) with highly stabilized loops flanking helix5 exhibited improved binding stability and affinity towards carbapenems, especially meropenem, OXA variants (e.g. OXA-10, OXA-251, OXA-48 and OXA-247) possessing highly flexibile loops flanking helix5 revealed their catalytic proficiency towards ceftazidime. Moreover, LIGPLOT and PROMALS3D jointly identified ten consensuses/conserved residues, viz. P68, A69, F72, K73, W105, V120, W164, L169, K216 and G218 to be critical for drug hydrolysis. Hence, novel inhibitors could be designed to target these sites.
      Graphical abstract image

      PubDate: 2016-06-13T10:05:05Z
  • Systematic Profiling of Chemotherapeutic Drug Response to EGFR Gatekeeper
           Mutation in Non-small Cell Lung Cancer
    • Abstract: Publication date: Available online 4 June 2016
      Source:Computational Biology and Chemistry
      Author(s): Jun Yao, Xiaojuan Zhao, Xi Ding
      The epidermal growth factor receptor (EGFR) targeted therapy has been established as a routine strategy for treating non-small cell lung cancer (NSCLC). However, the gatekeeper mutation T790M in EGFR active site can confer generic resistance to tyrosine kinase inhibitors (TKIs), largely limiting the clinical applications of chemotherapeutic drugs in NSCLC. Here, a combined method of computational analysis and growth inhibition assay was described to systematically investigate the molecular response profile of wild-type–sparing and mutant-resistant inhibitors to the EGFR T790M mutation. The profile is highly consistent with previous clinical observations; three first-line chemotherapeutic drugs Gefitinib, Erlotinib and Lapatinib are established with acquired resistance upon the mutation. In addition, it was found that the alkaloid compound K252a, a Staurosporine analog isolated from Nocardiopisis sp., can selectively target the EGFR T790M mutant over wild-type kinase (23-fold selectivity), suggesting that the compound is good lead candidate for development of T790M mutant-selective inhibitors. Structural analysis revealed that the mutation-resulting Met790 residue does not induce steric hindrance to the EGFR T790M–K252a complex system, while a number of hydrophobic forces, van der Waals contacts and S⋯π interactions are observed between the aromatic rings of K252a and the sulfhydryl group of Met790, contributing considerable stabilization energy to the system.
      Graphical abstract image

      PubDate: 2016-06-07T09:58:56Z
  • A theoretical study on the electronic structures and equilibrium constants
           evaluation of Deferasirox iron complexes
    • Abstract: Publication date: Available online 1 June 2016
      Source:Computational Biology and Chemistry
      Author(s): Samie Salehi, Amir Shokooh Saljooghi, Mohammad Izadyar
      Elemental iron is essential for cellular growth and homeostasis but it is potentially toxic to the cells and tissues. Excess iron can contribute in tumor initiation and tumor growth. Obviously, in iron overload issues using an iron chelator in order to reduce iron concentration seems to be vital. This study presents the density functional theory calculations of the electronic structure and equilibrium constant for iron-deferasirox (Fe-DFX) complexes in the gas phase, water and DMSO. A comprehensive study was performed to investigate the Deferasirox-iron complexes in chelation therapy. Calculation was performed in CAMB3LYP/6-31G(d,p) to get the optimized structures for iron complexes in high and low spin states. Natural bond orbital and quantum theory of atoms in molecules analyses was carried out with B3LYP/6-311G(d,p) to understand the nature of complex bond character and electronic transition in complexes. Electrostatic potential effects on the complexes were evaluated using the CHELPG calculations. The results indicated that higher affinity for Fe (III) is not strictly a function of bond length but also the degree of Fe–X (X=O,N) covalent bonding. Based on the quantum reactivity parameters which have been investigated here, it is possible reasonable design of the new chelators to improve the chelator abilities.
      Graphical abstract image

      PubDate: 2016-06-02T09:52:28Z
  • Chemical Reaction Optimization for solving Shortest Common Supersequence
    • Abstract: Publication date: Available online 31 May 2016
      Source:Computational Biology and Chemistry
      Author(s): C.M. Khaled Saifullah, Md. Rafiqul Islam
      Shortest Common Supersequence (SCS) is a classical NP-hard problem, where a string to be constructed that is the supersequence of a given string set. The SCS problem has an enormous application of data compression, query optimization in the database and different bioinformatics activities. Due to NP-hardness, the exact algorithms fail to compute SCS for larger instances. Many heuristics and meta-heuristics approaches were proposed to solve this problem. In this paper, we propose a meta-heuristics approach based on Chemical Reaction Optimization, CRO_SCS that is designed inspired by the nature of the chemical reactions. For different optimization problems like 0-1 knapsack, quadratic assignment, global numeric optimization problems CRO algorithm shows very good performance. We have redesigned the reaction operators and a new reform function to solve the SCS problem. The outcomes of the proposed CRO_SCS algorithm are compared with those of the enhanced beam search (IBS_SCS), deposition and reduction (DR), ant colony optimization (ACO) and artificial bee colony (ABC) algorithms. The length of supersequence, execution time and standard deviation of all related algorithms show that CRO_SCS gives better results on the average than all other algorithms.
      Graphical abstract image Highlights

      PubDate: 2016-06-02T09:52:28Z
  • Increasing thermal stability and catalytic activity of glutamate
           decarboxylase in E. coli: An in silico study
    • Abstract: Publication date: Available online 31 May 2016
      Source:Computational Biology and Chemistry
      Author(s): Yasaman Tavakoli, Abolghasem Esmaeili, Hossein Saber
      Glutamate decarboxylase (GAD) is an enzyme that converts L-glutamate to gamma amino butyric acid (GABA) that is a widely used drug to treat mental disorders like Alzheimer’s disease. In this study for the first time point mutation was performed virtually in the active site of the E. coli GAD in order to increase thermal stability and catalytic activity of the enzyme. Energy minimization and addition of water box were performed using GROMACS 5.4.6 package. PoPMuSiC 2.1 web server was used to predict potential spots for point mutation and Modeller software was used to perform point mutation on three dimensional model. Molegro virtual docker software was used for cavity detection and stimulated docking study. Results indicate that performing mutation separately at positions 164, 302, 304, 393, 396, 398 and 410 increase binding affinity to substrate. The enzyme is predicted to be more thermo- stable in all 7 mutants based on ΔΔG value.
      Graphical abstract image

      PubDate: 2016-06-02T09:52:28Z
  • Molecular dynamics and high throughput binding free energy calculation of
           anti-actin anticancer drugs—New insights for better design
    • Abstract: Publication date: Available online 24 May 2016
      Source:Computational Biology and Chemistry
      Author(s): L. Roopa, R. Pravin Kumar, L.M.M. Sudheer Mohammed
      Actin cytoskeleton plays an important role in cancerous cell progression. Till date many anticancer toxins are discovered that binds to different sites of actin. Mechanism of action of these toxins varies with respect to the site where they bind to actin. Latrunculin A (LAT) binds closely to nucleotide binding site and Reidispongiolide binds to the barbed end of actin. LAT is reported to reduce the displacement of domain 2 with respect to domain 1 and allosterically modulate nucleotide exchange. On the other hand Reidispongiolide binds with the higher affinity to actin and competes with the DNaseI binding loop once the inter-monomer interaction has been formed. Evolving better actin binders being the aim of this study we conducted a comparative molecular dynamics of these two actin-drug complexes and actin complexed with ATP alone, 50ns each. High throughput binding free energy calculations in conjugation with the high-throughput MD simulations was used to predict modifications in these two renowned anti-actin anticancer drugs for better design. Per residue energy profiling that contribute to free energy of binding shows that there is an unfavourable energy at the site where Asp157 interacts with 2-thiazolidinone moiety of LAT. Similarly, unfavourable energies are reported near macrocyclic region of Reidispongiolide specifically near carbons 7, 11 & 25 and tail region carbons 27 & 30. These predicted sites can be used for modifications and few of these are discussed in this work based on the interactions with the binding site residues. The study reveals specific interactions that are involved in the allosteric modulation of ATP by these two compounds. Glu207 closely interacting with LAT A initiates the allosteric effect on ATP binding site specifically affecting residues Asp184, Lys215 and Lys336. RGA bound actin shows high anti-correlated motions between sub domain 3 and 4. Unlike LAT A, Reidispongiolide induces a flat structure of actin which definitely should affect actin polymerisation and lead to disassembly of actin filaments.
      Graphical abstract image

      PubDate: 2016-05-28T09:34:06Z
  • Conformational Difference between Two Subunits in Flavin Mononucleotide
           Binding Protein Dimers from Desulfobivrio vugaris (MF): Molecular Dynamics
    • Abstract: Publication date: Available online 27 May 2016
      Source:Computational Biology and Chemistry
      Author(s): Nadtanet Nunthaboot, Kiattisak Lugsanangarm, Somsak Pianwanit, Sirirat Kokpol, Fumio Tanaka, Takeshi Nakanishi, Masaya Kitamura
      The structural and dynamical properties of five FMN binding protein (FBP) dimers, WT (wild type), E13K (Glu13 replaced by Lys), E13R (Glu13 replaced by Arg), E13T (Glu13 replaced by Thr) and E13Q (Glu13 replaced by Gln), were investigated using a method of molecular dynamics simulation (MDS). In crystal structures, subunit A (Sub A) and subunit B (Sub B) were almost completely equivalent in all of the five FBP dimers. However, the predicted MDS structures of the two subunits were not equivalent in solution, revealed by the distances and inter-planar angles between isoalloxazine (Iso) and aromatic amino acids (Trp32, Tyr35 and Trp106) as well as the hydrogen bonding pairs between Iso and nearby amino acids. Residue root of mean square fluctuations (RMSF) also displayed considerable differences between Sub A and Sub B and in the five FBP dimers. The dynamics of the whole protein structures were examined with the distance (RNN) between the peptide N atom of the N terminal (Met1) and the peptide N atom of the C terminal (Leu122). Water molecules were rarely accessible to Iso in all FBP dimers which are in contrast with other flavoenzymes.
      Graphical abstract image

      PubDate: 2016-05-28T09:34:06Z
  • Designing Peptide Inhibitor of Insulin Receptor to Induce Diabetes
           Mellitus Type 2 in Animal Model Mus musculus
    • Abstract: Publication date: Available online 27 May 2016
      Source:Computational Biology and Chemistry
      Author(s): Galuh W. Permatasari, Didik H. Utomo, Nashi Widodo
      A designing peptide as agent for inducing diabetes mellitus type 2 (T2DM) in an animal model is challenging. The computational approach provides a sophisticated tool to design a functional peptide that may block the insulin receptor activity. The peptide that able to inhibit the binding between insulin and insulin receptor is a warrant for inducing T2DM. Therefore, we designed a potential peptide inhibitor of insulin receptor as an agent to generate T2DM animal model by bioinformatics approach. The peptide has been developed based on the structure of insulin receptor binding site of insulin and then modified it to obtain the best properties of half life, hydrophobicity, antigenicity, and stability binding into insulin receptor. The results showed that the modified peptide has characteristics 100hours half-life, high-affinity −95.1±20, and high stability 28.17 in complex with the insulin receptor. Moreover, the modified peptide has molecular weight 4420.8g/Mol and has no antigenic regions. Based on the molecular dynamic simulation, the complex of modified peptide-insulin receptor is more stable than the commercial insulin receptor blocker. This study suggested that the modified peptide has the promising performance to block the insulin receptor activity that potentially induce diabetes mellitus type 2 in mice.
      Graphical abstract image

      PubDate: 2016-05-28T09:34:06Z
  • Design, Synthesis and Computational evaluation of a novel intermediate
           salt of N-cyclohexyl-N-(cyclohexylcarbamoyl)-4-(trifluoromethyl) benzamide
           as potential Potassium channel blocker in Epileptic paroxysmal seizures
    • Abstract: Publication date: Available online 20 May 2016
      Source:Computational Biology and Chemistry
      Author(s): V. Natchimuthu, Srinivas Bandaru, Anuraj Nayarisseri, S. Ravi
      The narrow therapeutic range and limited pharmacokinetics of available Antiepileptic drugs (AEDs) have raised serious concerns in the proper management of epilepsy. To overcome this, the present study attempts to identify a candidate molecule targeting voltage gated potassium channels anticipated to have superior pharmacological than existing potassium channel blockers. The compound was synthesized by reacting (S)-(+)-2,3-Dihydro-1H-pyrrolo[2,1-c][1,4] benzodiazepine5,11(10H,11aH)-dione with 4-(Trifluoromethyl) benzoic acid (C8H5F3O2) in DMF and N,N'-Dicyclohexylcarbodiimide (DCC) which lead to the formation of an intermediate salt of N-cyclohexyl-N-(cyclohexylcarbamoyl)-4-(trifluoromethyl)benzamide with a perfect crystalline structure. The structure of the compound was characterized by FTIR, 1H-NMR and 13C-NMR analysis. The crystal structure is confirmed by single crystal X-ray diffraction analysis. The Structure-Activity Relationship (SAR) studies revealed that substituent of fluoro or trifluoromethyl moiety into the compound had a great effect on the biological activity in comparison to clinically used drugs. Employing computational approaches the compound was further tested for its affinity against potassium protein structure by molecular docking in addition, bioactivity and ADMET properties were predicted through computer aided programs.
      Graphical abstract image

      PubDate: 2016-05-23T09:19:10Z
  • Molecular cloning, computational analysis and expression pattern of
           forkhead box l2 (Foxl2) gene in Catfish
    • Abstract: Publication date: Available online 18 May 2016
      Source:Computational Biology and Chemistry
      Author(s): Irfan Ahmad Bhat, Mohd Ashraf Rather, Jaffer Yousuf Dar, Rupam Sharma
      Foxl2 belongs to forkhead/HNF-3-related family of transcription factors which is involved in ovarian differentiation and development. In present study, the Foxl2 mRNA was cloned from ovary of C. batrachus. The full length cDNA sequence of the Foxl2 was 1056bp which consists of 5' (41bp) and 3' (106bp) non-coding regions, as well as a 909bp of open reading frame (ORF) that encodes 302 amino acids. The putative protein was having the theoretical molecular weight (MW) of 34.018kD and a calculated isoelectric point (pI) of 9.38. There were 11 serine (Ser), 5 threonine (Thr), and 5 tyrosine (Tyr) phosphorylation sites and 2 putative N-glycosylation sites on the predicted protein. The ligand binding sites were predicted to be present on amino acids 42, 49, 50, 91, 92 and 95 respectively. The signal peptide analysis predicted that C. batrachus Foxl2 is a non-secretory protein. The hydropathy profile of Foxl2 protein revealed that this protein is hydrophilic in nature. Protein-protein interaction demonstrated that Foxl2 protein chiefly interacts with cytochrome P450 protein family. The mRNA transcript analysis of various tissues indicated that the C. batrachus Foxl2 mRNA was more expressed in the brain, pituitary and ovary in female while, the former two tissues and testis showed low expression in male. This study provides a basis for further structural and functional exploration of the Foxl2 from C. batrachus, including its deduced protein and its signal transduction function.
      Graphical abstract image

      PubDate: 2016-05-23T09:19:10Z
  • Small molecule ligand docking to genotype specific bundle structures of
           hepatitis C virus (HCV) p7 protein
    • Abstract: Publication date: Available online 20 May 2016
      Source:Computational Biology and Chemistry
      Author(s): Niklas Laasch, Monoj Mon Kalita, Stephen Griffin, Wolfgang B. Fischer
      The genome of hepatitis C virus encodes for an essential 63 amino acid polytopic protein p7 of most likely two transmembrane domains (TMDs). The protein is identified to self-assemble thereby rendering lipid membranes permeable to ions. A series of small molecules such as adamantanes, imino sugars and guanidinium compounds are known to interact with p7. A set of 9 of these small molecules is docked against hexameric bundles of genotypes 5a (bundle-5a) and 1b (bundle-1b) using LeadIT. Putative sites for bundle-5a are identified within the pore and at pockets on the outside of the bundle. For bundle-1b preferred sites are found at the site of the loops. Binding energies are in favour of the guanidinium compounds. Rescoring of the identified poses with HYDE reveals a dehydration penalty for the guanidinium compounds, leaving the adamantanes and imino sugar in a better position. Binding energies calculated by HYDE and those by LeadIT indicate that all compounds are moderate binders.
      Graphical abstract image

      PubDate: 2016-05-23T09:19:10Z
    • Abstract: Publication date: Available online 17 May 2016
      Source:Computational Biology and Chemistry
      Author(s): Ramesh itteboina, Srilata Ballu, Sree Kanth Sivan, Vijjulatha Manga
      Janus kinase 1 (JAK 1) plays a critical role in initiating responses to cytokines by the JAK − signal transducer and activator of transcription (JAK-STAT). This controls survival, proliferation and differentiation of a variety of cells. Docking, 3D quantitative structure activity relationship (3D-QSAR) and molecular dynamics (MD) studies were performed on a series of Imidazo-pyrrolopyridine derivatives reported as JAK 1 inhibitors. QSAR model was generated using 30 molecules in the training set; developed model showed good statistical reliability, which is evident from r2 ncv and r2 loo values. The predictive ability of this model was determined using a test set of 13 molecules that gave acceptable predictive correlation (r2 Pred) values. Finally, molecular dynamics simulation was performed to validate docking results and MM/GBSA calculations. This facilitated us to compare binding free energies of cocrystal ligand and newly designed molecule R1. The good concordance between the docking results and CoMFA/CoMSIA contour maps afforded obliging clues for the rational modification of molecules to design more potent JAK 1 inhibitors.
      Graphical abstract image

      PubDate: 2016-05-18T09:02:33Z
  • Hidden Heterogeneity of Transcription Factor Binding Sites: A Case Study
           of SF-1
    • Abstract: Publication date: Available online 7 May 2016
      Source:Computational Biology and Chemistry
      Author(s): V.G. Levitsky, D.Yu. Oshchepkov, N.V. Klimova, E.V Ignatieva, G.V. Vasiliev, V.M. Merkulov, T.I. Merkulova
      Steroidogenic factor 1 (SF-1) belongs to a small group of the transcription factors that bind DNA only as a monomer. Three different approaches—Sitecon, SiteGA, and oPWM—constructed using the same training sample of experimentally confirmed SF-1 binding sites have been used to recognize these sites. The appropriate prediction thresholds for recognition models have been selected. Namely, the thresholds concordant by false positive or negative rates for various methods were used to optimize the discrimination of steroidogenic gene promoters from the datasets of non-specific promoters. After experimental verification, the models were used to analyze the ChIP-seq data for SF-1. It has been shown that the sets of sites recognized by different models overlap only partially and that an integration of these models allows for identification of SF-1 sites in up to 80% of the ChIP-seq loci. The structures of the sites detected using the three recognition models in the ChIP-seq peaks falling within the [–5000, +5000] region relative to the transcription start sites (TSS) extracted from the FANTOM5 project have been analyzed. The MATLIGN classified the frequency matrices for the sites predicted by oPWM, Sitecon, and SiteGA into two groups. The first group is described by oPWM/Sitecon and the second, by SiteGA. Gene ontology (GO) analysis has been used to clarify the differences between the sets of genes carrying different variants of SF-1 binding sites. Although this analysis in general revealed a considerable overlap in GO terms for the genes carrying the binding sites predicted by oPWM, Sitecon, or SiteGA, only the last method elicited notable trend to terms related to negative regulation and apoptosis. The results suggest that the SF-1 binding sites are different in both their structure and the functional annotation of the set of target genes correspond to the predictions by oPWM+Sitecon and SiteGA. Further application of Homer software for de novo identification of enriched motifs in ChIP-Seq data for SF-1ChIP-seq dataset gave the data similar to oPWM+Sitecon.
      Graphical abstract image

      PubDate: 2016-05-08T08:43:54Z
    • Abstract: Publication date: Available online 7 May 2016
      Source:Computational Biology and Chemistry
      Author(s): Tariq Mahmood, Najeeb Ullah Bakht, Ejaz Aziz
      Apple is the fourth most important fruit crop grown in temperate areas of the world belongs to the family Rosaceae. In the present study, the promoter (∼1000bp) region of atpB gene was used to evaluate the genetic diversity and phylogeny of six local apple varieties. atpB gene is one of the large chloroplastic region which encodes β-subunit of ATP synthase and previously it had been used largely in phylogenetic studies. During the present study, atpB promoter was amplified, sequenced and analyzed using various bioinformatics tools including Place Signal Scan, MEGA6 and BLASTn. During the phylogenetic analysis, obtained phylogram divided the studied varieties into two clusters revealing the monophyletic origin of studied apple varieties. Pairwise distance revealed moderate genetic diversity that ranges from 0.047-0.170 with an average of 0.101. While identifying different cis-acting elements present in the atpB promoter region, results exhibited the occurrence of 56 common and 20 unique cis-regulatory elements among studied varieties. The identified cis-acting regulatory elements were mapped as well. It was observed that Kala Kulu has the highest unique features with reference to the availability of cis-acting elements. Moreover, the possible functions of all regulatory elements present on the promoter sequence of atpB gene were predicted based on already reported information regarding their in vivo role.
      Graphical abstract image

      PubDate: 2016-05-08T08:43:54Z
  • Guest Editorial for the 14th Asia Pacific Bioinformatics Conference
    • Abstract: Publication date: Available online 13 April 2016
      Source:Computational Biology and Chemistry
      Author(s): Lu Tian, Jijun Tang, Yi-Ping Phoebe Chen

      PubDate: 2016-04-17T07:59:36Z
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