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  Subjects -> ENGINEERING (Total: 2265 journals)
    - CHEMICAL ENGINEERING (188 journals)
    - CIVIL ENGINEERING (179 journals)
    - ELECTRICAL ENGINEERING (99 journals)
    - ENGINEERING (1210 journals)
    - ENGINEERING MECHANICS AND MATERIALS (384 journals)
    - HYDRAULIC ENGINEERING (55 journals)
    - INDUSTRIAL ENGINEERING (60 journals)
    - MECHANICAL ENGINEERING (90 journals)

CHEMICAL ENGINEERING (188 journals)                     

Showing 1 - 0 of 0 Journals sorted alphabetically
AATCC Journal of Research     Full-text available via subscription   (Followers: 3)
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: 5)
Advanced Chemical Engineering Research     Open Access   (Followers: 12)
Advanced Powder Technology     Hybrid Journal   (Followers: 12)
Advances in Applied Ceramics     Hybrid Journal   (Followers: 4)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 22)
Advances in Chemical Engineering and Science     Open Access   (Followers: 33)
Advances in Polymer Technology     Hybrid Journal   (Followers: 12)
African Journal of Pure and Applied Chemistry     Open Access   (Followers: 6)
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: 8)
Anti-Corrosion Methods and Materials     Hybrid Journal   (Followers: 5)
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: 9)
Brazilian Journal of Chemical Engineering     Open Access   (Followers: 3)
Bulletin of Chemical Reaction Engineering & Catalysis     Open Access  
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: 3)
Chemical and Petroleum Engineering     Hybrid Journal   (Followers: 10)
Chemical and Process Engineering     Open Access   (Followers: 6)
Chemical and Process Engineering Research     Open Access   (Followers: 8)
Chemical Engineering & Technology     Hybrid Journal   (Followers: 31)
Chemical Engineering and Processing: Process Intensification     Hybrid Journal   (Followers: 17)
Chemical Engineering and Science     Open Access   (Followers: 6)
Chemical Engineering Communications     Hybrid Journal   (Followers: 11)
Chemical Engineering Journal     Hybrid Journal   (Followers: 22)
Chemical Engineering Research and Design     Hybrid Journal   (Followers: 20)
Chemical Engineering Research Bulletin     Open Access   (Followers: 2)
Chemical Engineering Science     Hybrid Journal   (Followers: 18)
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: 140)
Chemical Society Reviews     Full-text available via subscription   (Followers: 39)
Chemical Technology     Open Access   (Followers: 5)
ChemInform     Hybrid Journal   (Followers: 4)
Chemistry & Industry     Hybrid Journal   (Followers: 2)
Chemistry Central Journal     Open Access   (Followers: 5)
Chemistry of Materials     Full-text available via subscription   (Followers: 149)
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: 4)
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: 4)
Indian Journal of Chemical Technology (IJCT)     Open Access   (Followers: 9)
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: 102)
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: 6)
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 Coatings     Open Access   (Followers: 4)
Journal of Crystallization Process and Technology     Open Access   (Followers: 6)
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 Fuels     Open Access  
Journal of Geochemical Exploration     Hybrid Journal  
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: 6)
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 Powder Technology     Open Access   (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: 237)
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 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  
Molecular Imprinting     Open Access  
MRS Communications     Hybrid Journal  
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: 102)
Polymer Bulletin     Hybrid Journal   (Followers: 7)
Polymer Composites     Hybrid Journal   (Followers: 13)
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: 54)
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: 1)
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: 0.688]   [H-I: 43]   [9 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 1476-9271
   Published by Elsevier Homepage  [2969 journals]
  • 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.
      Graphical abstract image

      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.
      Graphical abstract image

      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.
      Graphical abstract image

      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.
      Graphical abstract image

      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.
      Graphical abstract image

      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
           pathway
    • 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.
      Graphical abstract image

      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.
      Graphical abstract image

      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
       
  • AN IN SILICO APPROACH TO ELUCIDATE STRUCTURE BASED FUNCTIONAL EVOLUTION OF
           OXACILLINASE
    • 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.
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      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
           Problem
    • 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.
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      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.
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      PubDate: 2016-05-28T09:34:06Z
       
  • Conformational Difference between Two Subunits in Flavin Mononucleotide
           Binding Protein Dimers from Desulfobivrio vugaris (MF): Molecular Dynamics
           Simulation
    • 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.
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      PubDate: 2016-05-28T09:34:06Z
       
  • IFC Editorial Board
    • Abstract: Publication date: June 2016
      Source:Computational Biology and Chemistry, Volume 62




      PubDate: 2016-05-28T09:34:06Z
       
  • Title page
    • Abstract: Publication date: June 2016
      Source:Computational Biology and Chemistry, Volume 62




      PubDate: 2016-05-28T09:34:06Z
       
  • Molecular docking study of natural alkaloids as multi-targeted hedgehog
           pathway inhibitors in cancer stem cell therapy
    • Abstract: Publication date: June 2016
      Source:Computational Biology and Chemistry, Volume 62
      Author(s): Mayank, Vikas Jaitak
      Cancer is responsible for millions of deaths throughout the world every year. Increased understanding as well as advancements in the therapeutic aspect seems suboptimal to restrict the huge deaths associated with cancer. The major cause responsible for this is high resistance as well as relapse rate associated with cancers. Several evidences indicated that cancer stem cells (CSC) are mainly responsible for the resistance and relapses associated with cancer. Furthermore, agents targeting a single protein seem to have higher chances of resistance than multitargeting drugs. According to the concept of network model, partial inhibition of multiple targets is more productive than single hit agents. Thus, by fusing both the premises that CSC and single hit anticancer drugs, both are responsible for cancer related resistances and screened alkaloids for the search of leads having CSC targeting ability as well as the capability to modulating multiple target proteins. The in silico experimental data indicated that emetine and cortistatin have the ability to modulate hedgehog (Hh) pathway by binding to sonic hedgehog (Hh), smoothened (Smo) and Gli protein, involved in maintenance CSCs. Furthermore, solamargine, solasonine and tylophorine are also seems to be good lead molecules targeting towards CSCs by modulating Hh pathway. Except solamargine and solasonine, other best lead molecules also showed acceptable in silico ADME profile. The predicted lead molecules can be suitably modified to get multitargeting CSC targeting agent to get rid of associate resistances.


      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.
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      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.
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      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
       
  • MOLECULAR DOCKING, 3D QSAR AND DYNAMICS SIMULATION STUDIES OF
           IMIDAZO-PYRROLOPYRIDINES AS JANUS KINASE 1 (JAK 1) INHIBITORS
    • 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.
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      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
       
  • Machine Learning Optimization of Cross Docking Accuracy
    • Abstract: Publication date: Available online 4 May 2016
      Source:Computational Biology and Chemistry
      Author(s): Esben J. Bjerrum
      Performance of small molecule automated docking programs has conceptually been divided into docking -, scoring -, ranking - and screening power, which focuses on the crystal pose prediction, affinity prediction, ligand ranking and database screening capabilities of the docking program, respectively. Benchmarks show that different docking programs can excel in individual benchmarks which suggests that the scoring function employed by the programs can be optimized for a particular task. Here the scoring function of Smina is re-optimized towards enhancing the docking power using a supervised machine learning approach and a manually curated database of ligands and cross docking receptor pairs. The optimization method does not need associated binding data for the receptor-ligand examples used in the data set and works with small train sets. The re-optimization of the weights for the scoring function results in a similar docking performance with regard to docking power towards a cross docking test set. A ligand decoy based benchmark indicates a better discrimination between poses with high and low RMSD. The reported parameters for Smina are compatible with Autodock Vina and represent ready-to-use alternative parameters for researchers who aim at pose prediction rather than affinity prediction.
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      PubDate: 2016-05-08T08:43:54Z
       
  • COMPUTATIONAL ANALYSIS OF atpB GENE PROMOTER FROM DIFFERENT PAKISTANI
           APPLE VARIETIES
    • 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.
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      PubDate: 2016-05-08T08:43:54Z
       
  • Cryptic tRNAs in chaetognath mitochondrial genomes
    • Abstract: Publication date: Available online 25 April 2016
      Source:Computational Biology and Chemistry
      Author(s): Roxane-Marie Barthélémy, Hervé Seligmann
      The chaetognaths constitute a small and enigmatic phylum of little marine invertebrates. Both nuclear and mitochondrial genomes have numerous originalities, some phylum-specific. Until recently, their mitogenomes seemed containing only one tRNA gene (trnMet), but a recent study found in two chaetognath mitogenomes two and four tRNA genes. Moreover, apparently two conspecific mitogenomes have different tRNA gene numbers (one and two). Reanalyses by tRNAscan-SE and ARWEN softwares of the five available complete chaetognath mitogenomes suggest numerous additional tRNA genes from different types. Their total number never reaches the 22 found in most other invertebrates using that genetic code. Predicted error compensation between codon-anticodon mismatch and tRNA misacylation suggests translational activity by tRNAs predicted solely according to secondary structure for tRNAs predicted by tRNAscan-SE, not ARWEN. Numbers of predicted stop-suppressor (antitermination) tRNAs coevolve with predicted overlapping, frameshifted protein coding genes including stop codons. Sequence alignments in secondary structure prediction with non-chaetognath tRNAs suggest that the most likely functional tRNAs are in intergenic regions, as regular mt-tRNAs. Due to usually short intergenic regions, generally tRNA sequences partially overlap with flanking genes. Some tRNA pairs seem templated by sense-antisense strands. Moreover, 16S rRNA genes, but not 12S rRNAs, appear as tRNA nurseries, as previously suggested for multifunctional ribosomal-like protogenomes.


      PubDate: 2016-04-29T08:19:10Z
       
  • Designing an efficient multi-epitope peptide vaccine against Vibrio
           cholerae via combined immunoinformatics and protein interaction based
           approaches
    • Abstract: Publication date: Available online 19 April 2016
      Source:Computational Biology and Chemistry
      Author(s): Navid Nezafat, Zeinab Karimi, Mahbobeh eslami, Milad Mohkam, Sanam Zandian, Younes Ghasemi
      Cholera continues to be a major global health concern. Among different Vibrio cholerae strains, only O1 and O139 cause acute diarrheal diseases that are related to epidemic and pandemic outbreaks. The currently available cholera vaccines are mainly lived and attenuated vaccines consisting of V. cholerae virulence factors such as toxin-coregulated pili (TCP), outer membrane proteins (Omps), and nontoxic cholera toxin B subunit (CTB). Nowadays, there is a great interest in designing an efficient epitope vaccine against cholera. Epitope vaccines consisting of immunodominant epitopes and adjuvant molecules enhance the possibility of inciting potent protective immunity. In this study, V. cholerae protective antigens (OmpW, OmpU, TcpA and TcpF) and the CTB, which is broadly used as an immunostimulatory adjuvant, were analyzed using different bioinformatics and immunoinformatics tools. The common regions between promiscuous epitopes, binding to various HLA-II supertype alleles, and B-cell epitopes were defined based upon the aforementioned protective antigens. The ultimately selected epitopes and CTB adjuvant were fused together using proper GPGPG linkers to enhance vaccine immunogenicity. A three-dimensional model of the thus constructed vaccine was generated using I-TASSER. The model was structurally validated using the ProSA-web error-detection software and the Ramachandran plot. The validation results indicated that the initial 3D model needed refinement. Subsequently, a high-quality model obtained after various refinement cycles was used for defining conformational B-cell epitopes. Several linear and conformational B-cell epitopes were determined within the epitope vaccine, suggesting likely antibody triggering features of our designed vaccine. Next, molecular docking was performed between the 3D vaccine model and the tertiary structure of the toll like receptor 2 (TLR2). To gain further insight into the interaction between vaccine and TLR2, molecular dynamics simulation was performed, corroborating stable vaccine-TLR2 binding. In sum, the results suggest that our designed epitope vaccine could incite robust long-term protective immunity against V. cholera.
      Graphical abstract image

      PubDate: 2016-04-21T08:04:44Z
       
  • Sequence-Based Analysis of 5′UTR and Coding Regions of CASP3 in
           terms of miRSNPs and SNPs in Targetting miRNAs
    • Abstract: Publication date: Available online 11 April 2016
      Source:Computational Biology and Chemistry
      Author(s): Sercan Ergun, Serdar Oztuzcu
      Apoptosis is described as a mechanism of cell death occurring after adequate cellular harm. Deregulation of apoptosis occurs in many human conditions such as autoimmune disorders, ischemic damage, neurodegenerative diseases and different cancer types. Information relating miRNAs to cancer is increasing. miRNAs can affect development of cancer via many different pathways, including apoptosis. Polymorphisms in miRNA genes or miRNA target sites (miRSNPs) can change miRNA activity. Although polymorphisms in miRNA genes are very uncommon, SNPs in miRNA-binding sites of target genes are quite common. Many researches have revelaed that SNPs in miRNA target sites improve or decrease the efficacy of the interaction between miRNAs and their target genes. Our aim was to specify miRSNPs on CASP3 gene (caspase-3) and SNPs in miRNA genes targeting 5'UTR and coding exons of CASP3, and evaluate the effect of these miRSNPs and SNPs of miRNA genes with respect to apoptosis. We detected 141 different miRNA binding sites (126 different miRNAs) and 7 different SNPs in binding sites of miRNA in 5′UTR and CDS of CASP3 gene. Intriguingly, miR-339-3p’s binding site on CASP3 has a SNP (rs35372903, G/A) on CASP3 5′UTR and its genomic sequence has a SNP (rs565188493, G/A) at the same nucleotide with rs35372903. Also, miR-339-3p has two other SNPs (rs373011663, C/T rs72631820, A/G) of which the first is positioned at the binding site. Here, miRSNP (rs35372903) at CASP3 5′UTR and SNP (rs565188493) at miR-339-3p genomic sequence cross-matches at the same site of binding region. Besides, miR-339-3p targets many apoptosis related genes (ZNF346, TAOK2, PIM2, HIP1, BBC3, TNFRSF25, CLCF1, IHPK2, NOL3) although it had no apoptosis related interaction proven before. This means that miR-339-3p may also have a critical effect on apoptosis via different pathways other than caspase-3. Hence, we can deduce that this is the first study demonstrating a powerful association between miR-339-3p and apoptosis upon computational analysis.
      Graphical abstract image

      PubDate: 2016-04-17T07:59:36Z
       
  • Guest Editorial for the 14th Asia Pacific Bioinformatics Conference
           (APBC2016)
    • 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
       
  • Genome-wide identification and expression analysis of swi1 genes in
           Boechera species
    • Abstract: Publication date: Available online 13 April 2016
      Source:Computational Biology and Chemistry
      Author(s): Fatih Sezer, Gözde Yüzbaşioğlu, Aslıhan Özbilen, Kemal M. Taşkin
      As a mode of reproduction in plants, apomixis leads to the generation of clones via seeds. Apomictic plants form viable diploid female gametes without meiosis (apomeiosis) and produce embryos without fertilization (parthenogenesis). Apomeiosis, as a major component of apomixis, has recently been reported in some Arabidopsis thaliana mutants; dyad mutants of SWI1 showed developmental processes common to apomeiosis, such as producing functional diploid gametes. However, the orthologs of SWI1 genes in natural apomicts has not been previously reported. To identify the relationship between the SWI1 gene and the apomeiosis process, we isolated and sequenced SWI1 orthologs from Boechera species, including apomictic and sexual species. Boechera species are close relatives of A. thaliana and thus are advantageous model species for apomixis research. The SWI1 cDNAs were obtained by RT-PCR from apomictic and sexual Boechera young flower buds. We sequenced partial SWI1 transcripts that were 650bp for B. holboellii and 684bp for B. stricta. These SWI1-like sequences showed 86% similarity for B. holboellii and 92% for B. stricta to the A. thaliana SWI1 transcript. We also used available genome data and amplified genomic sequences for SWI1 orthologs in B. holboellii and B. stricta. The predicted proteins contain a phospholipase C domain and a nuclear localization signal. Sequence analysis did not show significant mutations related to apomixis, and phylogenetic analysis showed that SWI1-like sequences were common across plant families, regardless of the presence of a sexual or apomictic reproduction system. We also investigated the expression levels of SWI1 mRNA in the B. holboellii and B. stricta young unopened flower buds and found that relatively high levels of expression occurred in apomicts.
      Graphical abstract image

      PubDate: 2016-04-17T07:59:36Z
       
  • Analysis of cis-acting regulatory elements of Respiratory burst oxidase
           homolog (Rboh) gene families in Arabidopsis and rice provides clues for
           their diverse functions
    • Abstract: Publication date: Available online 13 April 2016
      Source:Computational Biology and Chemistry
      Author(s): Gurpreet Kaur, Pratap Kumar Pati
      NADPH oxidase (NOX) is a critical enzyme in the production of reactive oxygen species (ROS). It catalyzes the production of apoplastic superoxide (O2 −), that regulates a wide array of biological functions in different organisms. Plant Noxes are homologs of catalytic subunit of mammalian NADPH oxidase and are well-known as Respiratory burst oxidase homologs (Rbohs). In recent years, there has been growing interest to study plant Noxes due to their versatile roles in plant systems. In the present work, comprehensive analysis on upstream regions from 10 Rbohs from Arabidopsis thaliana and 9 from Oryza sativa japonica was conducted. The distribution of various cis-elements, CpG islands and tandem repeats were analyzed to uncover the 5′ regulatory region in wide array of functions from Rbohs. Information retrieved from cis-elements analysis was also correlated with the microarray data. Present study which involves uncovering transcription regulatory elements provided vital clues for diverse functions of plant Rbohs.
      Graphical abstract image

      PubDate: 2016-04-17T07:59:36Z
       
  • A Computational Method for Prediction of rSNPs in Human Genome
    • Abstract: Publication date: Available online 4 April 2016
      Source:Computational Biology and Chemistry
      Author(s): Rong Li, Qiuqiang Han, Jun Liu, Jiguang Zheng, Ruiling Liu
      Regulatory single nucleotide polymorphisms (rSNPs) in human genome are thought to be responsible for phenotypic differences, including susceptibility to diseases and treatment outcomes, even they do not change any gene product. However, a genome-wide search for rSNPs has not been properly addressed so far. In this work, a computational method for rSNP identification is proposed. As background SNPs far outnumber rSNPs, an ensemble method is applied to handle imbalanced data, which firstly converts an unbalanced dataset into several balanced ones and then models for every balanced dataset. Two major types of features are extracted, that are sequence based features and allele-specific based features. Then random forest is applied to build the recognition model for each balanced dataset. Finally, ensemble strategies are adopted to combine the result of each model together. We have tested our method on a set of experimentally verified rSNPs, and leave-one-out cross-validation result shows that our method can achieve accuracy with sensitivity of 73.8%, specificity of 71.8% and the area under ROC curve (AUC) is 0.756. In addition, our method is threshold free and doesn’t rely on data of regulatory elements, thus it will have better adaptability when facing different data scenarios. The original data and the source matlab codes involved are available at https://sourceforge.net/projects/rsnpdect/.
      Graphical abstract image

      PubDate: 2016-04-05T05:12:06Z
       
  • Exploring the inhibitory potential of bioactive compound from Luffa
           acutangula against NF-κB − A molecular docking and dynamics
           approach
    • Abstract: Publication date: Available online 31 March 2016
      Source:Computational Biology and Chemistry
      Author(s): Ramar Vanajothi, Pappu Srinivasan
      Nuclear factor kappa B (NF-κB) is a transcription factor, plays a crucial role in the regulation of various physiological processes such as differentiation, cell proliferation and apoptosis. It also coordinates the expression of various soluble proinflammatory mediators like cytokines and chemokines. The 1, 8-dihydroxy-4-methylanthracene-9, 10-dione (DHMA) was isolated from Luffa acutangala and its in vitro cytotoxic activity against NCI-H460 cells was reported earlier. It also effectively induces apoptosis through suppressing the expression NF-κB protein. Based on experimental evidence, the binding affinity of compound 1 with NF-κB p50 (monomer) and NF-κB-DNA was investigated using molecular docking and its stability was confirmed through molecular dynamic simulation. The reactivity of the compound was evaluated using density functional theory (DFT) calculation. From the docking results, we noticed that the hydroxyl group of DHMA forms hydrogen bond interactions with polar and negatively charged amino acid Tyr57 and Asp239 and the protein-ligand complex was stabilized through pi-pi stacking with the help of polar amino acid His114, which plays a key role in binding of NF-κB to DNA at a site of DNA-binding region (DBR). The result indicates that the isolated bioactive compound DHMA might have altered the binding affinity between DNA and NF-κB. These findings suggest that potential use of DHMA in cancer chemoprevention and therapeutics.
      Graphical abstract image

      PubDate: 2016-04-01T05:06:40Z
       
  • Experimental and molecular dynamics studies showed the CBP KIX mutation
           affects the stability of CBP:c-Myb complex
    • Abstract: Publication date: Available online 21 March 2016
      Source:Computational Biology and Chemistry
      Author(s): Anne Odoux, Darren Jindal, Tamara C. Tamas, Benjamin W.H. Lim, Drake Pollard, Wu Xu
      The coactivators CBP (CREBBP) and its paralog p300 (EP300), two conserved multi-domain proteins in eukaryotic organisms, regulate gene expression in part by binding DNA-binding transcription factors. It was previously reported that the CBP/p300 KIX domain mutant (Y650A, A654Q and Y658A) altered both c-Myb-dependent gene activation and repression, and the mice with these three point mutations had reduced numbers of platelets, B cells, T cells, and red blood cells. Here, our transient transfection assays demonstrated that the mouse embryonic fibroblast cells containing the same mutations in the KIX domain and without wild-type allele of either CBP or p300, showed a decreased c-Myb-mediated transcription. Dr. Wright’s group solved a 3-D structure of mouse CBP:c-Myb complex using NMR method. To take advantage of the experimental structure and function data, and improved theoretical calculation methods, we performed MD simulations of CBP KIX, CBP KIX with the mutations, and c-Myb, as well as binding energy analysis for both the wild-type and mutant complexes. The binding between CBP and c-Myb is mainly mediated by a shallow hydrophobic groove in the center where the side-chain of Leu302 of c-Myb plays an essential role and two salt bridges at the two ends. We found that the KIX mutations slightly decreased stability of the CBP:c-Myb complex as demonstrated by higher binding energy calculated using either MM/PBSA or MM/GBSA methods. More specifically, the KIX mutations affected the two salt bridges between CBP and c-Myb (CBP-R646 and c-Myb-E306; CBP-E665 and c-Myb-R294). Our studies also revealed differing dynamics of the hydrogen bonds between CBP-R646 and c-Myb-E306, and between CBP-E665 and c-Myb-R294 caused by the CBP KIX mutations. In the wild-type CBP:c-Myb complex, both the hydrogen bonds stayed relatively stable. In contrast, in the mutant CBP:c-Myb complex, hydrogen bonds between R646 and E306 showed an increasing trend followed by a decreasing trend and hydrogen bonds between E665:R294 pair exhibited a fast decreasing trend over time during MD simulations. In addition, our data showed that the KIX mutations attenuate CBP’s hydrophobic interaction with Leu302 of c-Myb. Furthermore, our 500-ns MD simulations showed that the CBP KIX with the mutations has slightly lower potential energy than the wild-type CBP. The CBP KIX structures with or without its interacting protein c-Myb are different for both the wild-type and mutant CBP KIX, and this is likewise the case for c-Myb with or without CBP, suggesting that presence of an interacting protein influences the structure of a protein. Taken together, these analyses will improve our understanding of the exact functions of CBP and its interaction with c-Myb.
      Graphical abstract image

      PubDate: 2016-03-24T04:37:44Z
       
  • A multilayer screening approach toward the discovery of novel Pf-DHFR
           inhibitors
    • Abstract: Publication date: Available online 22 March 2016
      Source:Computational Biology and Chemistry
      Author(s): Sourav Bagchi, Manoj Kumar, Anuj Sharmaa
      A small yet diverse xanthone library was build and computationally docked against wild type Pf-DHFR by Molegro Virtual Docker (MolDock). For analysis of results an integrated approach based on re-ranking, scaling (based on heavy atom counts), pose clustering and visual inspection was implemented. Standard methods such as self-docking (for docking), EF analysis, average rank determinations (for size normalization), and cluster quality indices (for pose clustering) were used for validation of results. Three compounds X5, X113A and X164B displayed contact footprints similar to the known inhibitors with good scores. Finally, 16 compounds were extracted from ZINC data base by similarity based screening, docking score and drug/lead likeness. Out of these 16 compounds, 11 displayed very close contact footprints to experimentally known inhibitors, indicating there potential utility in further drug discovery efforts.
      Graphical abstract image

      PubDate: 2016-03-24T04:37:44Z
       
  • Dynamic characterization of HLA-B*44 Alleles: A comparative molecular
           dynamics simulation study
    • Abstract: Publication date: Available online 18 March 2016
      Source:Computational Biology and Chemistry
      Author(s): Pemra Özbek
      Human Leukocyte Antigens (HLA) are highly polymorphic proteins that play a key role in the immune system. HLA molecule is present on the cell membrane of antigen-presenting cells of the immune system and presents short peptides, originating from the proteins of invading pathogens or self-proteins, to the T-cell Receptor (TCR) molecule of the T-cells. In this study, peptide-binding characteristics of HLA-B*44:02, 44:03, 44:05 alleles bound to three nonameric peptides were studied using molecular dynamics simulations. Polymorphisms among these alleles (Asp116Tyr and Asp156Leu) result in major differences in the allele characteristics. While HLA-B*44:02 (Asp116, Asp156) and HLA-B*44:03 (Asp116, Leu156) depend on tapasin for efficient peptide loading, HLA-B*44:05 (Tyr116, Asp156) is tapasin independent. On the other hand, HLA-B*44:02 and HLA-B*44:03 mismatch is closely related to transplant rejection and acute-graft-versus-host disease. In order to understand the dynamic characteristics, the simulation trajectories were analyzed by applying Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuation (RMSF) calculations and hydrogen bonding analysis. Binding dynamics of the three HLA-B*44 alleles and peptide sequences are comparatively discussed. In general, peptide binding stability is found to depend on the peptide rather than the allele type for HLA-B*44 alleles.
      Graphical abstract image

      PubDate: 2016-03-20T04:27:19Z
       
  • IFC Editorial Board
    • Abstract: Publication date: April 2016
      Source:Computational Biology and Chemistry, Volume 61




      PubDate: 2016-03-20T04:27:19Z
       
  • Title page
    • Abstract: Publication date: April 2016
      Source:Computational Biology and Chemistry, Volume 61




      PubDate: 2016-03-20T04:27:19Z
       
  • Zooming-in on cancer metabolic rewiring with tissue specific
           constraint-based models
    • Abstract: Publication date: Available online 14 March 2016
      Source:Computational Biology and Chemistry
      Author(s): Marzia Di Filippo, Riccardo Colombo, Chiara Damiani, Dario Pescini, Daniela Gaglio, Marco Vanoni, Lilia Alberghina, Giancarlo Mauri
      The metabolic rearrangements occurring in cancer cells can be effectively investigated with a Systems Biology approach supported by metabolic network modeling. We here present tissue-specific constraint-based core models for three different types of tumors (liver, breast and lung) that serve this purpose. The core models were extracted and manually curated from the corresponding genome-scale metabolic models in the Human Metabolic Atlas database with a focus on the pathways that are known to play a key role in cancer growth and proliferation. Along similar lines, we also reconstructed a core model from the original general human metabolic network to be used as a reference model. A comparative Flux Balance Analysis between the reference and the cancer models highlighted both a clear distinction between the two conditions and a heterogeneity within the three different cancer types in terms of metabolic flux distribution. These results emphasize the need for modeling approaches able to keep up with this tumoral heterogeneity in order to identify more suitable drug targets and develop effective treatments. According to this perspective, we identified key points able to reverse the tumoral phenotype towards the reference one or vice-versa.
      Graphical abstract image Highlights

      PubDate: 2016-03-16T04:17:04Z
       
  • Using propensity score adjustment method in genetic association studies
    • Abstract: Publication date: Available online 3 March 2016
      Source:Computational Biology and Chemistry
      Author(s): Amrita Sengupta Chattopadhyay, Ying-Chao Lin, Ai-Ru Hsieh, Chien-Ching Chang, Ie-Bin Lian, Cathy S.J. Fann
      Background The statistical tests for single locus disease association are mostly under-powered. If a disease associated causal single nucleotide polymorphism (SNP) operates essentially through a complex mechanism that involves multiple SNPs or possible environmental factors, its effect might be missed if the causal SNP is studied in isolation without accounting for these unknown genetic influences. In this study, we attempt to address the issue of reduced power that is inherent in single point association studies by accounting for genetic influences that negatively impact the detection of causal variant in single point association analysis. In our method we use Propensity Score (PS) to adjust for the effect of SNPs that influence the marginal association of a candidate marker. These SNPs might be in linkage disequilibrium (LD) and/or epistatic with the target-SNP and have a joint interactive influence on the disease under study. We therefore propose a Propensity Score Adjustment Method (PSAM) as a tool for dimension reduction to improve the power for single locus studies through an estimated PS to adjust for influence from these SNPs while regressing disease status on the target-genetic locus. The degree of freedom of such a test is therefore always restricted to 1. Results We assess PSAM under the null hypothesis of no disease association to affirm that it correctly controls for the type-I-error rate (<0.05). PSAM displays reasonable power (>70%) and shows an average of 15% improvement in power as compared with commonly-used logistic regression method and PLINK under most simulated scenarios. Using the open-access Multifactor Dimensionality Reduction dataset, PSAM displays improved significance for all disease loci. Through a whole genome study, PSAM was able to identify 21 less significant SNPs from the GAW16 NARAC dataset by reducing the original trend-test p-values from within 0.001 and 0.05 to less than 0.0009, and among which 6 SNPs were further found to be associated with immunity and inflammation. Conclusions PSAM improves the significance of single-locus association of causal SNPs which have had marginal single point association by adjusting for influence from other SNPs in a dataset. This would explain part of the missing heritability without increasing the complexity of the model due to huge multiple testing scenarios. The newly reported SNPs from GAW16 data would provide evidences for further research to elucidate the etiology of Rheumatoid Arthritis. PSAM is proposed as an exploratory tool that would be complementary to other existing methods. A downloadable user friendly program, PSAM, written in SAS, is available for public use.
      Graphical abstract image

      PubDate: 2016-03-08T03:38:24Z
       
  • Animal inference on human mitochondrial diseases
    • Abstract: Publication date: Available online 16 February 2016
      Source:Computational Biology and Chemistry
      Author(s): Francesco Nardi, Francesco Frati, Pietro Liò
      Several pathological mutations in the human mitochondrial genome have been characterized based on medical, genetic and biochemical evidence. The observation that the structure and core functions of the mitochondrial genome are conserved from animals to man suggests that the analysis of animal variation may be informative to further characterize, and possibly predict, human pathological variants.


      PubDate: 2016-02-18T02:48:23Z
       
 
 
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