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CHEMICAL ENGINEERING (153 journals)                  1 2     

ACS Combinatorial Science     Full-text available via subscription   (Followers: 8)
Acta Crystallographica Section B: Structural Science, Crystal Engineering and Materials     Hybrid Journal   (Followers: 3)
Acta Polymerica     Hybrid Journal   (Followers: 6)
Additives for Polymers     Full-text available via subscription   (Followers: 19)
Adhesion Adhesives & Sealants     Hybrid Journal   (Followers: 4)
Advanced Chemical Engineering Research     Open Access   (Followers: 8)
Advanced Powder Technology     Hybrid Journal   (Followers: 12)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 15)
Advances in Chemical Engineering and Science     Open Access   (Followers: 21)
Advances in Polymer Technology     Hybrid Journal   (Followers: 11)
African Journal of Pure and Applied Chemistry     Open Access   (Followers: 2)
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: 10)
Anti-Corrosion Methods and Materials     Hybrid Journal   (Followers: 4)
Applied Petrochemical Research     Open Access   (Followers: 3)
Asia-Pacific Journal of Chemical Engineering     Hybrid Journal   (Followers: 6)
Biochemical Engineering Journal     Hybrid Journal   (Followers: 8)
Biomass Conversion and Biorefinery     Partially Free   (Followers: 5)
BMC Chemical Biology     Open Access   (Followers: 4)
Brazilian Journal of Chemical Engineering     Open Access   (Followers: 2)
Bulletin of the Chemical Society of Ethiopia     Open Access   (Followers: 1)
Carbohydrate Polymers     Hybrid Journal   (Followers: 8)
Catalysts     Open Access   (Followers: 6)
Chemical and Petroleum Engineering     Hybrid Journal   (Followers: 7)
Chemical and Process Engineering     Open Access   (Followers: 3)
Chemical and Process Engineering Research     Open Access   (Followers: 5)
Chemical Communications     Full-text available via subscription   (Followers: 29)
Chemical Engineering & Technology     Hybrid Journal   (Followers: 24)
Chemical Engineering and Processing: Process Intensification     Hybrid Journal   (Followers: 10)
Chemical Engineering and Science     Open Access   (Followers: 2)
Chemical Engineering Communications     Hybrid Journal   (Followers: 10)
Chemical Engineering Journal     Hybrid Journal   (Followers: 18)
Chemical Engineering Research and Design     Hybrid Journal   (Followers: 15)
Chemical Engineering Science     Hybrid Journal   (Followers: 10)
Chemical Geology     Hybrid Journal   (Followers: 9)
Chemical Papers     Hybrid Journal   (Followers: 3)
Chemical Product and Process Modeling     Full-text available via subscription   (Followers: 3)
Chemical Reviews     Full-text available via subscription   (Followers: 264)
Chemical Society Reviews     Full-text available via subscription   (Followers: 27)
Chemical Technology     Open Access   (Followers: 4)
ChemInform     Hybrid Journal   (Followers: 3)
Chemistry & Industry     Hybrid Journal   (Followers: 2)
Chemistry Central Journal     Open Access   (Followers: 5)
Chemistry of Materials     Full-text available via subscription   (Followers: 178)
Chemometrics and Intelligent Laboratory Systems     Hybrid Journal   (Followers: 6)
ChemSusChem     Hybrid Journal   (Followers: 7)
Chinese Chemical Letters     Full-text available via subscription   (Followers: 1)
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  
Coloration Technology     Hybrid Journal   (Followers: 1)
Computational Biology and Chemistry     Hybrid Journal   (Followers: 8)
Computer Aided Chemical Engineering     Full-text available via subscription   (Followers: 2)
Computers & Chemical Engineering     Hybrid Journal   (Followers: 6)
Corrosion Reviews     Full-text available via subscription   (Followers: 4)
Crystal Research and Technology     Hybrid Journal   (Followers: 2)
Current Opinion in Chemical Engineering     Open Access   (Followers: 3)
Education for Chemical Engineers     Hybrid Journal   (Followers: 4)
European Polymer Journal     Hybrid Journal   (Followers: 41)
Fibers and Polymers     Full-text available via subscription   (Followers: 3)
Focusing on Modern Food Industry     Open Access   (Followers: 3)
Frontiers of Chemical Science and Engineering     Hybrid Journal   (Followers: 1)
Geochemistry International     Hybrid Journal  
Handbook of Powder Technology     Full-text available via subscription   (Followers: 2)
High Performance Polymers     Hybrid Journal  
Indian Chemical Engineer     Hybrid Journal   (Followers: 3)
Indian Journal of Chemical Technology (IJCT)     Open Access   (Followers: 12)
Industrial & Engineering Chemistry     Full-text available via subscription   (Followers: 9)
Industrial & Engineering Chemistry Research     Full-text available via subscription   (Followers: 16)
Industrial Chemistry Library     Full-text available via subscription   (Followers: 4)
International Journal of Chemical and Petroleum Sciences     Open Access   (Followers: 1)
International Journal of Chemical Engineering     Open Access   (Followers: 6)
International Journal of Chemical Reactor Engineering     Full-text available via subscription   (Followers: 3)
International Journal of Chemical Technology     Open Access   (Followers: 3)
International Journal of Chemoinformatics and Chemical Engineering     Full-text available via subscription   (Followers: 2)
International Journal of Food Science     Open Access   (Followers: 2)
International Journal of Industrial Chemistry     Open Access  
International Journal of Polymeric Materials     Hybrid Journal   (Followers: 3)
International Journal of Science and Engineering     Open Access   (Followers: 7)
International Journal of Waste Resources     Open Access   (Followers: 4)
ISRN Chemical Engineering     Open Access   (Followers: 4)
ISRN Polymer Science     Open Access   (Followers: 11)
Journal of Applied Crystallography     Hybrid Journal   (Followers: 4)
Journal of Applied Electrochemistry     Hybrid Journal   (Followers: 6)
Journal of Applied Polymer Science     Hybrid Journal   (Followers: 168)
Journal of Biomaterials Science, Polymer Edition     Hybrid Journal   (Followers: 8)
Journal of Chemical & Engineering Data     Full-text available via subscription   (Followers: 6)
Journal of Chemical Ecology     Hybrid Journal   (Followers: 1)
Journal of Chemical Engineering     Open Access   (Followers: 3)
Journal of Chemical Engineering and Materials Science     Open Access  
Journal of Chemical Science and Technology     Open Access   (Followers: 1)
Journal of Chemical Sciences     Partially Free   (Followers: 15)
Journal of Chemical Technology & Biotechnology     Hybrid Journal   (Followers: 2)
Journal of Chemical Theory and Computation     Full-text available via subscription   (Followers: 9)
Journal of Coatings     Open Access   (Followers: 2)
Journal of Crystallization Process and Technology     Open Access   (Followers: 5)
Journal of Food Measurement and Characterization     Hybrid Journal  
Journal of Fuel Chemistry and Technology     Full-text available via subscription   (Followers: 5)
Journal of Fuels     Open Access  
Journal of Geochemical Exploration     Hybrid Journal  

        1 2     

Journal Cover Computational Biology and Chemistry
   Journal TOC RSS feeds Export to Zotero [10 followers]  Follow    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
     ISSN (Print) 1476-9271
     Published by Elsevier Homepage  [2563 journals]   [SJR: 0.558]   [H-I: 39]
  • Molecular dynamics simulations of lectin domain of FimH and
           Immunoinformatics for the design of potential vaccine candidates
    • Abstract: Publication date: Available online 15 August 2014
      Source:Computational Biology and Chemistry
      Author(s): Muthukumar Singaravelu , Anitha Selvan , Sharmila Anishetty
      Adhesion of Uropathogenic E.coli (UPEC) to uroepithelial cell receptors is facilitated through the lectin domain of FimH adhesin. In the current study, Molecular Dynamics (MD) simulations were performed for the lectin domain of FimH from UPEC J96. The high affinity state lectin domain was found to be stable and rigid during the simulations. Further, based on conserved subsequences around one of the disulphide forming cysteines, two sequence motifs were designed. An immunoinformatics approach was utilized to identify linear and discontinuous epitopes for the lectin domain of FimH. We propose that the accessibility of predicted epitopes should also be assessed in a dynamic aqueous environment to evaluate the potential of vaccine candidates. Since MD simulation data enables assessing the accessibility in a dynamic environment, we evaluated the accessibility of the top ranked discontinuous and linear epitopes using structures obtained at every nanosecond (ns) in the 1 – 20ns MD simulation timeframe. Knowledge gained in this study has a potential utility in the design of vaccine candidates for Urinary Tract Infection (UTI).
      Graphical abstract image

      PubDate: 2014-08-18T20:11:46Z
  • Circular code motifs in the ribosome decoding center
    • Abstract: Publication date: Available online 4 August 2014
      Source:Computational Biology and Chemistry
      Author(s): Karim El Soufi , Christian J. Michel
      A translation (framing) code based on the circular code was proposed in Michel (2012) with the identification of X circular code motifs (X motifs shortly) in the bacterial rRNA of Thermus thermophilus, in particular in the ribosome decoding center. Three classes of X motifs are now identified in the rRNAs of bacteria Escherichia coli and Thermus thermophilus, archaea Pyrococcus furiosus, nuclear eukaryotes Saccharomyces cerevisiae, Triticum aestivum and Homo sapiens, and chloroplast Spinacia oleracea. The universally conserved nucleotides A1492 and A1493 in all studied rRNAs (bacteria, archaea, nuclear eukaryotes and chloroplasts) belong to X motifs (called m AA). The conserved nucleotide G530 in rRNAs of bacteria and archaea belongs to X motifs (called m G). Furthermore, the X motif m G is also found in rRNAs of nuclear eukaryotes and chloroplasts. Finally, a potentially important X motif, called m, is identified in all studied rRNAs. With the available crystallographic structures of the Protein Data Bank PDB, we also show that these X motifs m AA, m G and m belong to the ribosome decoding center of all studied rRNAs with possible interaction with the mRNA X motifs and the tRNA X motifs. The three classes of X motifs identified here in rRNAs of several and different organisms strengthen the concept of translation code based on the circular code.
      Graphical abstract image

      PubDate: 2014-08-06T19:31:13Z
  • Title page
    • Abstract: Publication date: August 2014
      Source:Computational Biology and Chemistry, Volume 51

      PubDate: 2014-08-02T19:02:24Z
  • IFC Editorial Board
    • Abstract: Publication date: August 2014
      Source:Computational Biology and Chemistry, Volume 51

      PubDate: 2014-08-02T19:02:24Z
  • Genome-wide identification and predictive modeling of lincRNAs
           polyadenylation in cancer genome
    • Abstract: Publication date: Available online 27 July 2014
      Source:Computational Biology and Chemistry
      Author(s): Shanxin Zhang , Jiuqiang Han , Dexing Zhong , Ruiling Liu , Jiguang Zheng
      Long noncoding RNAs (lncRNAs) play essential regulatory roles in the human cancer genome. Many identified lncRNAs are transcribed by RNA polymerase II in which they are polyadenylated, whereby the long intervening noncoding RNAs (lincRNAs) have been widely used for the researches of lncRNAs. To date, the mechanism of lincRNAs polyadenylation related to cancer is rarely fully understood yet. In this paper, first we reported a comprehensive map of global lincRNAs polyadenylation sites (PASs) in five human cancer genomes; second we proposed a grouping method based on the pattern of genes expression and the manner of alternative polyadenylation (APA); third we investigated the distribution of motifs surrounding PASs. Our analysis reveals that about 70% of PASs are located in the sense strand of lincRNAs. Also more than 90% PASs in the antisense strand of lincRNAs are located in the intron regions. In addition, around 40% of lincRNA genes with PASs have APA sites. Four obvious motifs, i.e. AATAAA, TTTTTTTT, CCAGSCTGG and RGYRYRGTGG, were detected in the sequences surrounding PASs in the normal and cancer tissues. Furthermore, a novel algorithm was proposed to recognize the lincRNAs PASs of tumor tissues based on support vector machine (SVM). The algorithm can achieve the accuracies up to 96.55% and 89.48% for identification the tumor lincRNAs PASs from the non-polyadenylation sites and the non-lincRNA PASs, respectively.
      Graphical abstract image

      PubDate: 2014-07-28T18:36:12Z
  • Advances in bioinformatics: Selected papers from APBC 2014
    • Abstract: Publication date: June 2014
      Source:Computational Biology and Chemistry, Volume 50
      Author(s): Shuigeng Zhou , Yi-Ping Phoebe Chen

      PubDate: 2014-07-25T18:10:58Z
  • IFC Editorial Board
    • Abstract: Publication date: June 2014
      Source:Computational Biology and Chemistry, Volume 50

      PubDate: 2014-07-25T18:10:58Z
  • Title page
    • Abstract: Publication date: June 2014
      Source:Computational Biology and Chemistry, Volume 50

      PubDate: 2014-07-25T18:10:58Z
  • Structure and evolution analysis of pollen receptor-like kinase in Zea
           mays and Arabidopsis thaliana
    • Abstract: Publication date: August 2014
      Source:Computational Biology and Chemistry, Volume 51
      Author(s): Dongxu Wang , He Wang , Muhammad Irfan , Mingxia Fan , Feng Lin
      Receptor-like kinase (RLKs) is an important member in protein kinase family which is widely involved in plant growth, development and defense responses. It is significant to analyze the kinase structure and evolution of pollen RLKs in order to study their mechanisms. In our study, 64 and 73 putative pollen RLKs were chosen from maize and Arabidopsis. Phylogenetic analysis showed that the pollen RLKs were conservative and might had existed before divergence between monocot and dicot which were mainly concentrated in RLCK-VII and LRR-III two subfamilies. Chromosomal localization and gene duplication analysis showed the expansion of pollen RLKs were mainly caused by segmental duplication. By calculating Ka/Ks value of extracellular domain, intracellular domain and kinase domain in pollen RLKs, we found that the pollen RLKs duplicated genes had mainly experienced the purifying selection, while maize might have experienced weaker purifying selection. Meanwhile, extracellular domain might have experienced stronger diversifying selection than intracellular domain in both species. Estimation of duplication time showed that the duplication events of Arabidopsis have occurred approximately between 18 and 69 million years ago, compared to 0.67–170 million years ago of maize.
      Graphical abstract image

      PubDate: 2014-07-25T18:10:58Z
  • Gene Cloning, Homology Comparison and Analysis of the Main Functional
           Structure Domains of beta Estrogen Receptor in Jining Grey Goat
    • Abstract: Publication date: Available online 1 June 2014
      Source:Computational Biology and Chemistry
      Author(s): Hai-gang Liu , Hong-mei Li , Shuying Wang , Libo Huang , Hui-jun Guo
      To clarify the molecular evolution and characteristic of beta estrogen receptor (ERβ) gene in Jining Grey goat in China, the entire ERβ gene from Jining Grey goat ovary was amplified, identified and sequenced, and the gene sequences were compared with those of other animals. Functional structural domains and variations in DNA binding domains (DBD) and ligand binding domains (LBD) between Jining Grey goat and Boer goat were analyzed. The results indicate that the ERβ gene in Jining Grey goat includes a 1584bp sequence with a complete open-reading-frame (ORF), encoding a 527 amino acid (aa) receptor protein. Compared to other species, the nucleotide homology is 73.9%-98.9% and the amino acid homology is 79.5%-98.5%. The main antigenic structural domains lie from the 97th aa to the 286th aa and from the 403rd aa to the 527th aa. The hydrophilicity and the surface probability of the structural domains are distributed throughout a range of amino acids. There are two different amino acids in the DBD and three different amino acids in the LBD between Jining Grey and Boer goats, resulting in dramatically different spatial structures for ERβ protein. These differences may explain the different biological activities of ERβ between the two goat species. This study firstly acquired the whole ERβ gene sequence of Jining Grey goat with a complete open reading frame, and analyzed its gene evolutionary relationship and predicted its mainly functional structural domains, which may very help for further understanding the genome evolution and gene diversity of goat ERβ.
      Graphical abstract image

      PubDate: 2014-06-05T14:50:14Z
  • In silico study of potential autoimmune threats from rotavirus infection
    • Abstract: Publication date: Available online 4 June 2014
      Source:Computational Biology and Chemistry
      Author(s): Tapati Sarkar , Sukhen Das , Papiya Nandy , Rahul Bhowmick , Ashesh Nandy
      Rotavirus, the major cause of infantile nonbacterial diarrhea, was found to be associated with development of diabetes-associated auto-antibodies. In our study we tried to find out further potential autoimmune threats of this virus using bioinformatics approach. We took rotaviral proteins to study similarity with Homo sapiens proteome and found most conserved structural protein VP6 matches at two regions with ryanodine receptor, an autoimmune target associated with myasthenia gravis. Myasthenia gravis, a chronic neurodegenerative auto immune disorder with no typical known reason, is characterized by fluctuating muscle weakness which is typically enhanced during muscular effort. Affected patients generate auto antibodies against mainly acetyl choline receptor and sarcoplasmic reticulum calcium-release channel protein ryanodine receptor. Further, we observed that two regions which matched with ryanodine receptor remain conserved in all circulating rotaviral strains and showed significant antigenecity with respect to myasthenia gravis associated HLA haplotypes. Overall, our study detected rotaviral VP6 as a potential threat for myasthenia gravis and enlighten an area of virus associated autoimmune research.
      Graphical abstract image

      PubDate: 2014-06-05T14:50:14Z
  • A Computational Prospect to Aspirin Side Effects: Aspirin and COX-1
           Interaction Analysis based on Non-Synonymous SNPs
    • Abstract: Publication date: Available online 2 June 2014
      Source:Computational Biology and Chemistry
      Author(s): Mojtabavi Naeini Marjan , Mesrian Tanha Hamzeh , Emamzadeh Rahman , Vallian Sadeq
      Aspirin (ASA) is a commonly used nonsteroidal anti-inflammatory drug (NSAID), which exerts its therapeutic effects through inhibition of cyclooxygenase (COX) isoform 2 (COX-2), while the inhibition of COX-1 by ASA leads to apparent side effects. In the present study, the relationship between COX-1 non-synonymous single nucleotide polymorphisms (nsSNPs) and Aspirin related side effects was investigated. The functional impacts of 37 nsSNPs on aspirin inhibition potency of COX-1 with COX-1/aspirin molecular docking were computationally analyzed, and each SNP was scored based on DOCK AMBER score. The data predicted that 22 nsSNPs could reduce COX-1 inhibition, while 15 nsSNPs showed increasing inhibition level in comparison to the regular COX-1 protein. In order to perform a comparing state, the AMBER scores for two Arg119 mutants (R119A and R119Q) were also calculated. Moreover, among nsSNP variants, rs117122585 represented the closest AMBER score to R119A mutant. A separate docking computation validated the score and represented a new binding position for ASA that acetyl group was located within the distance of 3.86 Å from Ser529 OH group. This could predict an associated loss of activity of ASA through this nsSNP variant. Our data represent a computational sub-population pattern for aspirin COX-1 related side effects, and provide basis for further research on COX-1/ASA interaction.
      Graphical abstract image

      PubDate: 2014-06-05T14:50:14Z
  • A computational method of predicting regulatory interactions in
           Arabidopsis based on gene expression data and sequence information
    • Abstract: Publication date: Available online 9 May 2014
      Source:Computational Biology and Chemistry
      Author(s): Xiaoqing Yu , Hongyun Gao , Xiaoqi Zheng , Chun Li , Jun Wang
      Inferring transcriptional regulatory interactions between transcription factors (TFs) and their targets has utmost importance for understanding the complex regulatory mechanisms in cellular system. In this paper, we introduced a computational method to predict regulatory interactions in Arabidopsis based on gene expression data and sequence information. Support vector machine (SVM) and Jackknife cross-validation test were employed to perform our method on a collected dataset including 178 positive samples and 1068 negative samples. Results showed that our method achieved an overall accuracy of 98.39% with the sensitivity of 94.88%, and the specificity of 93.82%, which suggested that our method can serve as a potential and cost-effective tool for predicting regulatory interactions in Arabidopsis.
      Graphical abstract image

      PubDate: 2014-05-10T10:33:11Z
  • Structural evaluation of BTK and PKCδ mediated phosphorylation of MAL
           at positions Tyr86 and Tyr106
    • Abstract: Publication date: Available online 19 April 2014
      Source:Computational Biology and Chemistry
      Author(s): Rehan Zafar Paracha , Amjad Ali , Jamil Ahmad , Riaz Hussain , Umar Niazi , Syed Aun Muhammad
      A number of diseases including sepsis, rheumatoid arthritis, diabetes, cardiovascular diseases and hyperinflammatory immune disorders have been associated with Toll like receptor (TLR) 2 and TLR4. Endogenous adaptor protein known as MyD88 Adapter–like protein (MAL) bind exclusively to the cytosolic portions of TLR2 and TLR4 to initiate downstream signalling. Brutons Tyrosine Kinase (BTK) and Protein Kinase C delta (PKCδ) have been implicated to phosphorylate MAL and activate it to initiate downstream signalling. BTK has been associated with phosphorylation at positions Tyr86 and Tyr106, necessary for the activation of MAL but definite residual target of PKCδ in MAL is still to be explored. To produce a better understanding of the functional domains involved in the formation of MAL-kinase complexes, computer-aided studies were used to characterize the protein-protein interactions (PPIs) of phosphorylated BTK and PKCδ with MAL. Docking and physicochemical studies indicated that BTK was involved in close contact with Tyr86 and Tyr106 of MAL whereas PKCδ may phosphorylate Tyr106 only. Moreover, the electrostatics charge distribution of binding interfaces of BTK and PKCδ were distinct but compatible with respective regions of MAL. Our results implicate that position of Tyr86 is specifically phosphorylated by BTK whereas Tyr106 can be phosphorylated by competitive action of both BTK and PKCδ. Additionally, the residues of MAL which are necessary for interaction with TLR2, TLR4, MyD88 and SOCS-1 also play their roles in maintaining interaction with kinases and can be targeted in future to reduce TLR2 and TLR4 induced pathological responses.
      Graphical abstract image Highlights

      PubDate: 2014-04-23T09:25:06Z
  • Investigation of phase shifts for different period lengths in the genomes
           of C.elegans, D.melanogaster and S.cerevisiae
    • Abstract: Publication date: Available online 13 April 2014
      Source:Computational Biology and Chemistry
      Author(s): Pugacheva Valentina , Frenkel Felix , Korotkov Eugene
      We describe a new mathematical method for finding very diverged short tandem repeats containing a single indel. The method involves comparison of two frequency matrices: a first matrix for a subsequence before shift and a second one for a subsequence after it. A measure of comparison is based on matrix similarity. The approach developed was applied to analysis of the genomes of C.elegans, D.melanogaster and S.cerevisiae. They were investigated regarding the presence of tandem repeats having repeat length equal to 2 and 4-11 nucleotides. A number of phase shift regions for these genomes was approximately 2.2×104, 1.5×104 and 1.7×102, respectively. Type I error was less than 5%. The mean length of fuzzy periodicity and phase shift regions was about 220 nucleotides. The regions of fuzzy periodicity having single insertion or deletion occupy substantial parts of the genomes: 5%, 3% and 0.3%, respectively. Only less than 10% of these regions have been detected previously. That is, the number of such regions in the genomes of C.elegans, D.melanogaster and S.cerevisiae is dramatically higher than it has been revealed by any known methods. We suppose that some found regions of fuzzy periodicity could be the regions for protein binding.
      Graphical abstract image

      PubDate: 2014-04-18T08:31:10Z
  • All-atomic Molecular Dynamic Studies of Human CDK8: Insight into the
           A-loop, Point Mutations and Binding with Its Partner CycC
    • Abstract: Publication date: Available online 3 April 2014
      Source:Computational Biology and Chemistry
      Author(s): Wu Xu , Benjamin Amire-Brahimi , Xiao-Jun Xie , Liying Huang , Jun-Yuan Ji
      The Mediator, a conserved multisubunit protein complex in eukaryotic organisms, regulates gene expression by bridging sequence-specific DNA-binding transcription factors to the general RNA polymerase II machinery. In yeast, Mediator complex is organized in three core modules (head, middle and tail) and a separable ‘CDK8 submodule’ consisting of four subunits including Cyclin-dependent kinase CDK8 (CDK8), Cyclin C (CycC), MED12, and MED13 The 3-D structure of human CDK8-CycC complex has been recently experimentally determined. To take advantage of this structure and the improved theoretical calculation methods, we have performed molecular dynamic simulations to study dynamics of CDK8 and two CDK8 point mutations (D173A and D189N), which have been identified in human cancers, with and without full length of the A-loop as well as the binding between CDK8 and CycC. We found that CDK8 structure gradually loses two helical structures during the 50-ns molecular dynamic simulation, likely due to the presence of the full-length A-loop. In addition, our studies showed the hydrogen bond occupation of the CDK8 A-loop increases during the first 20-ns MD simulation and stays stable during the later 30-ns MD simulation. Four residues in the A-loop of CDK8 have high hydrogen bond occupation, while the rest residues have low or no hydrogen bond occupation. The hydrogen bond dynamic study of the A-loop residues exhibits three types of changes: increasing, decreasing, and stable. Furthermore, the 3-D structures of CDK8 point mutations D173A, D189N, T196A and T196D have been built by molecular modeling and further investigated by 50-ns molecular dynamic simulations. D173A has the highest average potential energy, while T196D has the lowest average potential energy, indicating that T196D is the most stable structure. Finally, we calculated theoretical binding energy of CDK8 and CycC by MM/PBSA and MM/GBSA methods, and the negative values obtained from both methods demonstrate stability of CDK8-CycC complex. Taken together, these analyses will improve our understanding of the exact functions of CDK8 and the interaction with its partner CycC.
      Graphical abstract image

      PubDate: 2014-04-04T04:24:48Z
  • IFC Editorial Board
    • Abstract: Publication date: April 2014
      Source:Computational Biology and Chemistry, Volume 49

      PubDate: 2014-03-31T02:29:03Z
  • Title page
    • Abstract: Publication date: April 2014
      Source:Computational Biology and Chemistry, Volume 49

      PubDate: 2014-03-31T02:29:03Z
  • Publisher Note
    • Abstract: Publication date: April 2014
      Source:Computational Biology and Chemistry, Volume 49

      PubDate: 2014-03-31T02:29:03Z
  • Genome-wide analysis and evolutionary study of sucrose non-fermenting
           1-related protein kinase 2 (SnRK2) gene family members in Arabidopsis and
    • Abstract: Publication date: April 2014
      Source:Computational Biology and Chemistry, Volume 49
      Author(s): Jayita Saha , Chitrita Chatterjee , Atreyee Sengupta , Kamala Gupta , Bhaskar Gupta
      The over-expression of plant specific SnRK2 gene family members by hyperosmotic stress and some by abscisic acid is well established. In this report, we have analyzed the evolution of SnRK2 gene family in different plant lineages including green algae, moss, lycophyte, dicot and monocot. Our results provide some evidences to indicate that the natural selection pressure had considerable influence on cis-regulatory promoter region and coding region of SnRK2 members in Arabidopsis and Oryza independently through time. Observed degree of sequence/motif conservation amongst SnRK2 homolog in all the analyzed plant lineages strongly supported their inclusion as members of this family. The chromosomal distributions of duplicated SnRK2 members have also been analyzed in Arabidopsis and Oryza. Massively Parallel Signature Sequencing (MPSS) database derived expression data and the presence of abiotic stress related promoter elements within the 1kb upstream promoter region of these SnRK2 family members further strengthen the observations of previous workers. Additionally, the phylogenetic relationships of SnRK2 have been studied in all plant lineages along with their respective exon–intron structural patterns. Our results indicate that the ancestral SnRK2 gene of land plants gradually evolved by duplication and diversification and modified itself through exon–intron loss events to survive under environmental stress conditions.
      Graphical abstract image

      PubDate: 2014-03-31T02:29:03Z
  • In-silico study of anti-carcinogenic Lysyl Oxidase-Like 2 inhibitors
    • Abstract: Publication date: Available online 20 March 2014
      Source:Computational Biology and Chemistry
      Author(s): Syed Aun Muhammad , Amjad Ali , Tariq Ismail , Rehan Zafar , Umair Ilyas , Jamil Ahmad
      Lysyl oxidase homolog 2 (LOXL2), also known as Lysyl oxidase-like protein 2 is recently been explored as regulator of carcinogenesis and has been shown to be involved in tumor progression and metastasis of several carcinomas. Therefore LOXL2 has been considered as potential therapeutic target. Doing so, its inhibitors as new chemotherapeutic lead molecules: 4-Amino-5-(2-Hydroxyphenyl)-1,2,4-Triazol-3-Thione (2a) and 4-(2-hydroxybenzalidine) amine-5-(2-hydroxy) phenyl-1,2,4-triazole-3-thiol (2b) are synthesized by fusion method (refluxed at 160°C). Spectral analysis of these triazole derivatives are characterized by FTIR and NMR. Active binding sites and quality of the LOXL2 model is assessed by Ramachandran plots and finally drug-target analysis is performed by computational virtual screening tools. Compounds 2a and 2b showed optimum target binding affinity with -6.2Kcal/mol and -8.9Kcal/mol binding energies. This in-silico study will add to our understanding of the drug designing and development, and to target cancer-causing proteins more precisely and quickly than before.

      PubDate: 2014-03-22T23:22:05Z
  • Determining common insertion sites based on retroviral insertion
           distribution across tumors
    • Abstract: Publication date: Available online 12 March 2014
      Source:Computational Biology and Chemistry
      Author(s): Feng Chen , Zhoufang Li , Yi-Ping Phoebe Chen
      A CIS (Common Insertion Site) indicates a genome region that is hit more frequently by retroviral insertions than expected by chance. Such a region is strongly related to cancer gene loci, which leads to the detection of cancer genes. An algorithm for detecting CISs should satisfy the following: 1) it does not require any prior knowledge of underlying insertion distribution; 2) it can resolve the insertion biases caused by hotspots; 3) it can detect CISs of any biological width; 4) it can identify noises resulting from statistic mistakes and non-CIS insertions; and 5) it can identify the widths of CISs as accurately as possible. We develop a method to resolve these difficulties. We verify a region's significance from two perspectives: distribution width and distribution depth. The former indicates how many insertions in a region while the latter evaluates the insertion distribution across the tumors in a region. We compare our method with kernel density estimation and sliding window on the simulated data, showing that our method not only identifies cancer-related insertions effectively, but also filters noises correctly. The experiments on the real data show that taking insertion distribution into account can highlight significant CISs. We detect 53 novel CISs, some of which have been proven correct by the biological literature.
      Graphical abstract image

      PubDate: 2014-03-14T22:32:16Z
  • An ensemble method for prediction of conformational B-cell epitopes from
           antigen sequences
    • Abstract: Publication date: Available online 18 February 2014
      Source:Computational Biology and Chemistry
      Author(s): Wei Zheng , Chen Zhang , Michelle Hanlon , Jishou Ruan , Jianzhao Gao
      Epitopes are immunogenic regions in antigen protein. Prediction of B-cell epitopes is critical for immunological applications. B-cell epitopes are categorized into linear and conformational. The majority of B-cell epitopes are conformational. Several machine learning methods have been proposed to identify conformational B-cell epitopes. However, the quality of these methods is not ideal. One question is whether or not the prediction of conformational B-cell epitopes can be improved by using ensemble methods. In this paper, we propose an ensemble method, which combined 12 support vector machine-based predictors, to predict the conformational B-cell epitopes, using an unbound dataset. AdaBoost and resampling methods are used to deal with an imbalanced labeled dataset. The proposed method achieves AUC of 0.642-0.672 on training dataset with 5-fold cross validation and AUC of 0.579-0.604 on test dataset. We also find some interesting results with the bound and unbound datasets. Epitopes are more accessible than non-epitopes, in bound and unbound datasets. Epitopes are also preferred in beta-turn, in bound and unbound datasets. The flexibility and polarity of epitopes are higher than non-epitopes. In a bound dataset, Asn (N), Glu (E), Gly (G), Lys (K), Ser (S), and Thr (T) are preferred in epitope regions, while Ala (A), Leu (L) and Val (V) are preferred in non-epitope regions. In the unbound dataset, Glu(E) and Lys(K) are preferred in epitope sites, while Leu(L) and Val(V) are preferred in non-epitiopes sites.

      PubDate: 2014-02-19T05:21:52Z
  • ISDTool: A computational model for predicting immunosuppressive domain of
    • Abstract: Publication date: Available online 12 February 2014
      Source:Computational Biology and Chemistry
      Author(s): Hongqiang Lv , Jiuqiang Han , Jun Liu , Jiguang Zheng , Dexing Zhong , Ruiling Liu
      Human endogenous retroviruses (HERVs) have been found to act as etiological cofactors in several chronic diseases, including cancer, autoimmunity and neurological dysfunction. Immunosuppressive domain (ISD) is a conserved region of transmembrane proteins (TM) in envelope gene (env) of retroviruses. In vitro and vivo, evidence has shown that retroviral TM is highly immunosuppressive and a synthetic peptide (CKS-17) that shows homology to ISD inhibits immune function. ISD is probably a potential pathogenic element in HERVs. However, only less than one hundred ISDs of HERVs have been annotated by researchers so far, and universal software for domain prediction could not achieve sufficient accuracy for specific ISD. In this paper, a computational model is proposed to identify ISD in HERVs based on genome sequences only. It has a classification accuracy of 97.9% using Jack-knife test. 117 HERVs families were scanned with the model, 1 002 new putative ISDs have been predicted and annotated in the human chromosomes. This model is also applicable to search for ISDs in human T-lymphotropic virus (HTLV), simian T-lymphotropic virus (STLV) and murine leukemia virus (MLV) because of the evolutionary relationship between endogenous and exogenous retroviruses. Furthermore, software named ISDTool has been developed to facilitate the application of the model. Datasets and the software involved in the paper are all available at
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      PubDate: 2014-02-15T02:49:12Z
  • IFC Editorial Board
    • Abstract: Publication date: February 2014
      Source:Computational Biology and Chemistry, Volume 48

      PubDate: 2014-02-11T22:22:37Z
  • Title page
    • Abstract: Publication date: February 2014
      Source:Computational Biology and Chemistry, Volume 48

      PubDate: 2014-02-11T22:22:37Z
  • Editorial
    • Abstract: Publication date: February 2014
      Source:Computational Biology and Chemistry, Volume 48
      Author(s): Wentian Li

      PubDate: 2014-02-11T22:22:37Z
  • Mode of action classification of chemicals using multi-concentration
           time-dependent cellular response profiles
    • Abstract: Publication date: Available online 5 February 2014
      Source:Computational Biology and Chemistry
      Author(s): Zhankun Xi , Swanand Khare , Aaron Cheung , Biao Huang , Tianhong Pan , Weiping Zhang , Fadi Ibrahim , Can Jin , Stephan Gabos
      In this paper, we present a new statistical pattern recognition method for classifying cytotoxic cellular responses to toxic agents. The advantage of the proposed method is to quickly assess the toxicity level of an unclassified toxic agent on human health by bringing cytotoxic cellular responses with similar patterns (Mode Of Action, MoOA) into the same class. The proposed method is a model-based hierarchical classification approach incorporating Principal Component Analysis (PCA) & Functional Data Analysis (FDA). The cytotoxic cell responses are represented by multi-concentration Time-dependent Cellular Response Profiles (TCRPs) which are dynamically recorded by using the xCELLigence Real-Time Cell Analysis High-Throughput (RTCA HT) system. The classification results obtained using our algorithm show satisfactory discrimination and are validated using biological facts by examining common chemical mechanisms of actions with treatment on human hepatocellular carcinoma cells (HepG2).
      Graphical abstract image Highlights

      PubDate: 2014-02-07T20:13:17Z
  • Affinity of HIV-1 antibody 2G12 with monosaccharides: A theoretical study
           based on explicit and implicit water models
    • Abstract: Publication date: Available online 4 February 2014
      Source:Computational Biology and Chemistry
      Author(s): Yuka Koyama , Kaori Ueno-Noto , Keiko Takano
      In order to develop potential ligands to HIV-1 antibody 2G12 toward HIV-1 vaccine, binding mechanisms of the antibody 2G12 with the glycan ligand of D-mannose and D-fructose were theoretically examined. D-fructose, whose molecular structure is slightly different from D-mannose, has experimentally shown to have stronger binding affinity to the antibody than that of D-mannose. To clarify the nature of D-fructose's higher binding affinity over D-mannose, we studied interaction between the monosaccharides and the antibody using ab initio fragment molecular orbital (FMO) method considering solvation effect as implicit model (FMO-PCM) as well as explicit water model. The calculated binding free energies of the glycans were qualitatively well consistent with the experimentally reported order of their affinities with the antibody 2G12. In addition, the FMO-PCM calculation elucidated the advantages of D-fructose over D-mannose in the solvation energy as well as the entropic contribution term obtained by MD simulations. The effects of explicit water molecules observed in the x-ray crystal structure were also scrutinized by means of FMO methods. Significant pair interaction energies among D-fructose, amino acids, and water molecules were uncovered, which indicated contributions from the water molecules to the strong binding ability of D-fructose to the antibody 2G12. These FMO calculation results of explicit water model as well as implicit water model indicated that the strong binding of D-fructose over D-mannose was due to the solvation effects on the D-fructose interaction energy.
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      PubDate: 2014-02-07T20:13:17Z
  • Fast detection of high-order epistatic interactions in genome-wide
           association studies using information theoretic measure
    • Abstract: Publication date: Available online 27 January 2014
      Source:Computational Biology and Chemistry
      Author(s): Sangseob Leem , Hyun-hwan Jeong , Jungseob Lee , Kyubum Wee , Kyung-Ah Sohn
      There are many algorithms for detecting epistatic interactions in GWAS. However, most of these algorithms are applicable only for detecting two-locus interactions. Some algorithms are designed to detect only two-locus interactions from the beginning. Others do not have limits to the order of interactions, but in practice take very long time to detect higher order interactions in real data of GWAS. Even the better ones take days to detect higher order interactions in WTCCC data. We propose a fast algorithm for detection of high order epistatic interactions in GWAS. It runs k-means clustering algorithm on the set of all SNPs. Then candidates are selected from each cluster. These candidates are examined to find the causative SNPs of k-locus interactions. We use mutual information from information theory as the measure of association between genotypes and phenotypes. We tested the power and speed of our method on extensive sets of simulated data. The results show that our method has more or equal power, and runs much faster than previously reported methods. We also applied our algorithm on each of seven diseases in WTCCC data to analyze up to 5-locus interactions. It takes only a few hours to analyze 5-locus interactions in one dataset. From the results we make some interesting and meaningful observations on each disease in WTCCC data. In this study, a simple yet powerful two-step approach is proposed for fast detection of high order epistatic interaction. Our algorithm makes it possible to detect high order epistatic interactions in GWAS in a matter of hours on a PC.

      PubDate: 2014-01-30T17:17:58Z
  • Improved homology model of cyclohexanone monooxygenase from Acinetobacter
           calcoaceticus based on multiple templates
    • Abstract: Publication date: Available online 28 January 2014
      Source:Computational Biology and Chemistry
      Author(s): Eduardo Bermúdez , Oscar N. Ventura , Leif A. Eriksson , Patricia Saenz-Méndez
      A new homology model of cyclohexanone monooxygenase (CHMO) from Acinetobacter calcoaceticus is derived based on multiple templates, and in particular the crystal structure of CHMO from Rhodococcus sp. The derived model was fully evaluated, showing that the quality of the new structure was improved over previous models. Critically, the nicotinamide cofactor is included in the model for the first time. Analysis of several molecular dynamics snapshots of intermediates in the enzymatic mechanism led to a description of key residues for cofactor binding and intermediate stabilization during the reaction, in particular Arg327 and the well known conserved motif (FxGxxxHxxxW) in Baeyer-Villiger monooxygenases, in excellent agreement with known experimental and computational data.
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      PubDate: 2014-01-30T17:17:58Z
  • lncRNAMap: A map of putative regulatory functions in the long non-coding
    • Abstract: Publication date: Available online 23 January 2014
      Source:Computational Biology and Chemistry
      Author(s): Wen-Ling Chan , Hsien-Da Huang , Jan-Gowth Chang
      Background Recent studies have demonstrated the importance of long non-coding RNAs (lncRNAs) in chromatin remodeling, and in transcriptional and post-transcriptional regulation. However, only a few specific lncRNAs are well understood, whereas others are completely uncharacterised. To address this, there is a need for user-friendly platform to studying the putative regulatory functions of human lncRNAs. Description lncRNAMap is an integrated and comprehensive database relating to exploration of the putative regulatory functions of human lncRNAs with two mechanisms of regulation, by encoding siRNAs and by acting as miRNA decoys. To investigate lncRNAs producing siRNAs that regulate protein-coding genes, lncRNAMap integrated small RNAs (sRNAs) that were supported by publicly available deep sequencing data from various sRNA libraries and constructed lncRNA-derived siRNA-target interactions. In addition, lncRNAMap demonstrated that lncRNAs can act as targets for miRNAs that would otherwise regulate protein-coding genes. Previously studies indicated that intergenic lncRNAs (lincRNAs) either positive or negative regulated neighboring genes, therefore, lncRNAMap surveyed neighboring genes within a 1 Mb distance from the genomic location of specific lncRNAs and provided the expression profiles of lncRNA and its neighboring genes. The gene expression profiles may supply the relationship between lncRNA and its neighboring genes. Conclusions lncRNAMap is a powerful user-friendly platform for the investigation of putative regulatory functions of human lncRNAs with producing siRNAs and acting as miRNA decoy. lncRNAMap is freely available on the web at ht*tp://

      PubDate: 2014-01-26T22:15:30Z
  • Predicting Essential Genes for Identifying Potential Drug Targets In
           Aspergillus fumigatus
    • Abstract: Publication date: Available online 23 January 2014
      Source:Computational Biology and Chemistry
      Author(s): Yao Lu , Jingyuan Deng , Judith C. Rhodes , Hui Lu , Long Jason Lu
      Background Aspergillus fumigatus (Af) is a ubiquitous and opportunistic pathogen capable of causing acute, invasive pulmonary disease in susceptible hosts. Despite current therapeutic options, mortality associated with invasive Af infections remains unacceptably high, increasing 357% since 1980. Therefore, there is an urgent need for the development of novel therapeutic strategies, including more efficacious drugs acting on new targets. Thus, as noted in a recent review, “the identification of essential genes in fungi represents a crucial step in the development of new antifungal drugs”. Expanding the target space by rapidly identifying new essential genes has thus been described as “the most important task of genomics-based target validation”. Results In previous research, we were the first to show that essential gene annotation can be reliably transferred between distantly related four Prokaryotic species. In this study, we extend our machine learning approach to the much more complex Eukaryotic fungal species. A compendium of essential genes is predicted in Af by transferring known essential gene annotations from another filamentous fungus N. crassa. This approach predicts essential genes by integrating diverse types of intrinsic and context-dependent genomic features encoded in microbial genomes. The predicted essential datasets contained 1,674 genes. We validated our results by comparing our predictions with known essential genes in Af, comparing our predictions with those predicted by homology mapping, and conducting conditional expressed alleles. We applied several layers of filters and selected a set of potential drug targets from the predicted essential genes. Finally, we have conducted wet lab knockout experiments to verify our predictions, which further validates the accuracy and wide applicability of the machine learning approach. Conclusions The approach presented here significantly extended our ability to predict essential genes beyond orthologs and made it possible to predict an inventory of essential genes in Eukaryotic fungal species, amongst which a preferred subset of suitable drug targets may be selected. By selecting the best new targets, we believe that resultant drugs would exhibit an unparalleled clinical impact against a naive pathogen population. Additional benefits that a compendium of essential genes can provide are important information on cell function and evolutionary biology. Furthermore, mapping essential genes to pathways may also reveal critical check points in the pathogen's metabolism. Finally, this approach is highly reproducible and portable, and can be easily applied to predict essential genes in many more pathogenic microbes, especially those unculturable.

      PubDate: 2014-01-26T22:15:30Z
  • Pharmacoepidemiological characterization of drug-inducedadverse reaction
           clusters towards understanding of their mechanisms
    • Abstract: Publication date: Available online 24 January 2014
      Source:Computational Biology and Chemistry
      Author(s): Sayaka Mizutani , Yousuke Noro , Masaaki Kotera , Susumu Goto
      A big challenge in pharmacology is the understanding of the underlying mechanisms that cause drug-induced adverse reactions (ADRs), which are in some cases similar to each other regardless of different drug indications, and are in other cases different regardless of same drug indications. The FDA Adverse Event Reporting System (FAERS) provides a variable resource for pharmacoepidemiology, the study of the uses and the effects of drugs in large human population. However, FAERS is a spontaneous reporting system that inevitably contains noise that deviates the application of conventional clustering approaches. By performing a biclustering analysis on the FAERS data we identified 163 biclusters of drug-induced adverse reactions, counting for 691 ADRs and 240 drugs in total, where the number of ADR occurrences are consistently high across the associated drugs. Medically similar ADRs are derived from several distinct indications for use in the majority (145/163=88%) of the biclusters, which enabled us to interpret the underlying mechanisms that lead to similar ADRs. Furthermore, we compared the biclusters that contain same drugs but different ADRs, finding the cases where the populations of the patients were different in terms of age, sex, and body weight. We applied a biclustering approach to catalogue the relationship between drugs and adverse reactions from a large FAERS data set, and demonstrated a systematic way to uncover the cases different drug administrations resulted in similar adverse reactions, and the same drug can cause different reactions dependent on the patients’ conditions.

      PubDate: 2014-01-26T22:15:30Z
  • Practical halving; the Nelumbo nucifera evidence on early eudicot
    • Abstract: Publication date: Available online 26 January 2014
      Source:Computational Biology and Chemistry
      Author(s): Chunfang Zheng , David Sankoff
      We present a stepwise optimal genome halving algorithm designed for large eukaryote genomes with largely single-copy genes, taking advantage of a signature pattern of paralog distribution in ancient polyploids. This is applied to the genome of Nelumbo nucifera, the sacred lotus, which is the descendant of a duplicated basal eudicot genome. In concert with the reconstructed ancestor of the grape, we investigate early events in eudicot evolution and show that the chromosome number of the common ancestor of lotus and grape was likely between 5 and 7. We show that the duplication of the ancestor of lotus and the triplication of the ancestor of grape were not closely preceded by any additional such event before the divergence of their two lineages.

      PubDate: 2014-01-26T22:15:30Z
  • Identification and characterization of lysine-methylated sites on histones
           and non-histone proteins
    • Abstract: Publication date: Available online 24 January 2014
      Source:Computational Biology and Chemistry
      Author(s): Tzong-Yi Lee , Cheng-Wei Chang , Cheng-Tzung Lu , Tzu-Hsiu Cheng , Tzu-Hao Chang
      Protein methylation is a kind of post-translational modification (PTM), and typically takes place on lysine and arginine amino acid residues. Protein methylation is involved in many important biological processes, and most recent studies focused on lysine methylation of histones due to its critical roles in regulating transcriptional repression and activation. Histones possess highly conserved sequences and are homologous in most species. However, there is much less sequence conservation among non-histone proteins. Therefore, mechanisms for identifying lysine-methylated sites may greatly differ between histones and non-histone proteins. Nevertheless, this point of view was not considered in previous studies. Here we constructed two support vector machine (SVM) models by using lysine-methylated data from histones and non-histone proteins for predictions of lysine-methylated sites. Numerous features, such as the amino acid composition (AAC) and accessible surface area (ASA), were used in the SVM models, and the predictive performance was evaluated using five-fold cross-validations. For histones, the predictive sensitivity was 85.62% and specificity was 80.32%. For non-histone proteins, the predictive sensitivity was 69.1% and specificity was 88.72%. Results showed that our model significantly improved the predictive accuracy of histones compared to previous approaches. In addition, features of the flanking region of lysine-methylated sites on histones and non-histone proteins were also characterized and are discussed. A gene ontology functional analysis of lysine-methylated proteins and correlations of lysine-methylated sites with other PTMs in histones were also analyzed in detail. Finally, a web server, MethyK, was constructed to identify lysine-methylated sites. MethK now is available at

      PubDate: 2014-01-26T22:15:30Z
  • Parallel molecular computation of modular-multiplication withtwo same
           inputs over finite field GF(2n) usingself-assembly of DNA tiles
    • Abstract: Publication date: Available online 23 January 2014
      Source:Computational Biology and Chemistry
      Author(s): Yongnan Li , Limin Xiao , Li Ruan
      Two major advantages of DNA computing — huge memory capacity and high parallelism — are being explored for large-scale parallel computing, mass data storage and cryptography. Tile assembly model is a highly distributed parallel model of DNA computing. Finite field GF(2 n ) is one of the most commonly used mathematic sets for constructing public-key cryptosystem. It is still an open question that how to implement the basic operations over finite field GF(2 n ) using DNA tiles. This paper proposes how the parallel tile assembly process could be used for computing the modular-square, modular-multiplication with two same inputs, over finite field GF(2 n ). This system could obtain the final result within less steps than another molecular computing system designed in our previous study, because square and reduction are executed simultaneously and the previous system computes reduction after calculating square. Rigorous theoretical proofs are described and specific computing instance is given after defining the basic tiles and the assembly rules. Time complexity of this system is 3n −1 and space complexity is 2n 2.
      Graphical abstract image Highlights

      PubDate: 2014-01-23T18:42:06Z
  • Effect of sampling on the extent and accuracy of the inferred genetic
           history of recombining genome
    • Abstract: Publication date: Available online 23 January 2014
      Source:Computational Biology and Chemistry
      Author(s): Daniel E. Platt , Filippo Utro , Laxmi Parida
      Accessible biotechnology is enabling the cataloging of genetic variants in individuals in populations at unprecedented scales. The use of phylogeny of the individuals within populations allows a model-based approach to studying these variations, which is important in understanding relationships between and across populations. For the somatic genome, however, the phylogeny must take recombinations (and other genetic mixing events) into account. Hence the resulting topology is more complex than a tree. Unlike a tree topology, it is not as apparent which events are visible from the extant samples. An earlier work presented a mathematical model (called the minimal descriptor) for teasing apart the inherent visible information from that which any specific algorithm might see. We use this framework to study the effect of sampling sizes on the overall inferred genetic history. In this paper, we seek to understand the extent, characteristics (in terms of recent versus ancient genetic events) and reliability of what was resolvable within field samples drawn from modern populations. We observed that most of the visible ancient events are recoverable from relatively small sample sizes. However, without identification of this relatively small minority of ancient genetic events, most of the signal will appear to reflect modern events and admixtures. We also found that the more ancient events are likely to be reproduced with higher fidelity between multiple samplings, and that the identified older events are less likely to yield false positive discrimination between populations. We conclude that a recombinant phylogenetic reconstruction is necessary to identify which markers are most likely to discriminate ancient events, and to discriminate between populations with lower risk of false positives. Secondly, on a broader note, this study also provides a general methodology for a critical assessment of the inferred common genetic history of populations (say, in plant cultivars or animal populations).
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      PubDate: 2014-01-23T18:42:06Z
  • piClust: A density based piRNA clustering algorithm
    • Abstract: Publication date: Available online 23 January 2014
      Source:Computational Biology and Chemistry
      Author(s): Inuk Jung , Jong Chan Park , Sun Kim
      Piwi-interacting RNAs (piRNAs) are recently discovered, endogenous small non-coding RNAs. piRNAs protect the genome from invasive transposable elements (TE) and sustain integrity of the genome in germ cell lineages. Due to lack of sequence conservation across species and poor sequence characteristics, such as length and 1T or 10A nucleotide bias, piRNAs are poorly characterized. Pioneering studies showed that piRNAs appear in clusters. Due to the lack of discriminating characteristics, piRNA cluster detection is the reliable method for detecting piRNA origins. Development of sophisticated computational methods for detecting piRNA clusters is needed. proTRAC, a state of the art method, detects piRNA clusters based on a probabilistic analysis with assumption of a uniform distribution. However, with careful investigation on data sets, we found that a uniform or any statistical distribution for detecting piRNA clusters may not be assumed. Furthermore, small RNA-seq data contains noisy data that was not carefully taken into account in previous studies. Our study was motivated due to unsuccessful cluster detection using proTRAC on our proprietary chicken germ cell line small RNA-seq data. To improve piRNA cluster identification, we used a density based clustering approach without assumption of any parametric distribution which is robust to noise in the data. In experiments with piRNA data from human, mouse, rat and chicken, piClust was able to detect piRNA clusters from total small RNA-seq data from germ cell lines, while proTRAC was not successful. piClust outperformed proTRAC in terms of sensitivity and running time (up to 200 folds). piClust is currently available as a web service at
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      PubDate: 2014-01-23T18:42:06Z
  • Gene expression regulation of the PF00480 or PF14340 domain proteins
           suggests their involvement in sulfur metabolism
    • Abstract: Publication date: Available online 22 January 2014
      Source:Computational Biology and Chemistry
      Author(s): Vassily A. Lyubetsky , Semen A. Korolev , Alexandr V. Seliverstov , Oleg A. Zverkov , Lev. I. Rubanov
      The paper studies proteins with domains PF00480 or PF14340, as well as some other poorly characterized proteins, encoded by genes associated with leader peptide genes containing a tract of cysteine codons. Such proteins are hypothetically regulated with cysteine-dependent transcription attenuation, namely the Rho-dependent or classic transcription attenuation. Cysteine is an important structural amino acid in various proteins and is required for synthesis of many sulfur-containing compounds, such as methionine, thiamine, glutathione, taurine, the lipoic acid, etc. Earlier a few species of mycobacteria were predicted by the authors to have cysteine-dependent regulation of operons containing the сysK gene. In E. coli this regulation is absent, and the same operon is regulated by the CysB transcription activator. The paper also studies Rho-dependent and classic transcription regulations in all annotated genes of mycobacteria available in GenBank and their orthologs in Actinomycetales. We predict regulations for many genes involved in sulfur metabolism and transport of sulfur-containing compounds; these regulations differ considerably among species. On the basis of predictions, we assign a putative role to proteins encoded by the regulated genes with unknown function, and also describe the structure of corresponding regulons, predict the lack of such regulations for many genes. Thus, all proteins with the uncharacterized Pfam domains PF14340 and PF00480, as well as some others, are predicted to be involved in sulfur metabolism. We also surmise the affinity of some transporters to sulfur-containing compounds. The obtained results considerably extend earlier large-scale studies of Rho-dependent and classic transcription attenuations.
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      PubDate: 2014-01-23T18:42:06Z
  • Deciphering Histone Code of Transcriptional Regulation in Malaria
           Parasites by Large-scale Data Mining
    • Abstract: Publication date: Available online 23 January 2014
      Source:Computational Biology and Chemistry
      Author(s): Haifen Chen , Stefano Lonardi , Jie Zheng
      Histone modifications play a major role in the regulation of gene expression. Evidence has been accumulated to show that histone modifications mediate biological processes such as transcription cooperatively. This has led to the hypothesis of ‘histone code’ which suggests that combinations of different histone modifications correspond to unique chromatin states and have distinct functions. In this paper, we propose a framework based on association rule mining to discover the potential regulatory relations between histone modifications and gene expression in Plasmodium falciparum. Our approach can output rules with statistical significance. Some of the discovered rules are supported by literature of experimental results. Moreover, we have also discovered de novo rules which can guide further research in epigenetic regulation of transcription. Based on our association rules we build a model to predict gene expression, which outperforms a published Bayesian network model for gene regulation by histone modifications. The results of our study reveal mechanisms for histone modifications to regulate transcription in large-scale. Among our findings, the cooperation among histone modifications provides new evidence for the hypothesis of histone code. Furthermore, the rules output by our method can be used to predict the change of gene expression.

      PubDate: 2014-01-23T18:42:06Z
  • Collective variable driven molecular dynamics to improve protein-protein
           docking scoring
    • Abstract: Publication date: Available online 18 January 2014
      Source:Computational Biology and Chemistry
      Author(s): Diego Masone , Solène Grosdidier
      In biophysics, the structural prediction of protein–protein complexes starting from the unbound form of the two interacting monomers is a major difficulty. Although current computational docking protocols are able to generate near-native solutions in a reasonable time, the problem of identifying near-native conformations from a pool of solutions remains very challenging. In this study we use molecular dynamics simulations driven by a collective reaction coordinate to optimize full hydrogen bond networks in a set of protein-protein docking solutions. The collective coordinate biases the system to maximize the formation of hydrogen bonds at the protein-protein interface as well as all over the structure. The reaction coordinate is therefore a measure for docking poses affinity and hence is used as scoring function to identify near-native conformations.
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      PubDate: 2014-01-20T17:24:07Z
  • Improving the prediction of chemotherapeutic sensitivity of tumors in
           breast cancer via optimizing the selection of candidate genes
    • Abstract: Publication date: Available online 1 January 2014
      Source:Computational Biology and Chemistry
      Author(s): Lina Jiang , Liqiu Huang , Qifan Kuang , Juan Zhang , Menglong Li , Zhining Wen , Li He
      Estrogen receptor status and the pathologic response to preoperative chemotherapy are two important indicators of chemotherapeutic sensitivity of tumors in breast cancer, which are used to guide the selection of specific regimens for patients. Microarray-based gene expression profiling, which is successfully applied to the discovery of tumor biomarkers and the prediction of drug response, was suggested to predict the cancer outcomes using the gene signatures differentially expressed between two clinical states. However, many false positive genes unrelated to the phenotypic differences will be involved in the lists of differentially expressed genes (DEGs) when only using the statistical methods for gene selection, e.g. Student's t test, and subsequently affect the performance of the predictive models. For the purpose of improving the prediction of clinical outcomes, we optimized the selection of DEGs by using a combined strategy, for which the DEGs were firstly identified by the statistical methods, and then filtered by a similarity profiling approach that used for candidate gene prioritization. In our study, we firstly verified the molecular functions of the DEGs identified by the combined strategy with the gene expression data generated in the microarray experiments of Si-Wu-Tang, which is a popular formula in traditional Chinese medicine. The results showed that, for Si-Wu-Tang experimental data set, the cancer-related signaling pathways were significantly enriched by gene set enrichment analysis when using the DEG lists generated by the combined strategy, confirming the potentially cancer-preventive effect of Si-Wu-Tang. To verify the performance of the predictive models in clinical application, we used the combined strategy to select the DEGs as features from the gene expression data of the clinical samples, which were collected from the breast cancer patients, and constructed models to predict the chemotherapeutic sensitivity of tumors in breast cancer. After refining the DEG lists by a similarity profiling approach, the Matthew's correlation coefficients of predicting estrogen receptor status and the pathologic response to preoperative chemotherapy with the DEGs selected by the fold change ranking were 0.770 and 0.428, respectively, and were 0.748 and 0.373 with the DEGs selected by SAM, respectively, which were generally higher than those achieved with unrefined DEG lists and those achieved by the candidate models in the second phase of Microarray Quality Control project (0.732 and 0.301, respectively). Our results demonstrated that the strategy of integrating the statistical methods with the gene prioritization methods based on similarity profiling was a powerful tool for DEG selection, which effectively improved the performance of prediction models in clinical applications and can guide the personalized chemotherapy better.
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      PubDate: 2014-01-02T22:17:02Z
  • Identification and Characterization of Potential Drug Targets by
           Subtractive Genome Analyses of Methicillin Resistant Staphylococcus aureus
    • Abstract: Publication date: Available online 5 December 2013
      Source:Computational Biology and Chemistry
      Author(s): Reaz Uddin , Kiran Saeed
      Methicillin resistant Staphylococcus aureus (MRSA) causes serious infections in humans and becomes resistant to a number of antibiotics. Due to the emergence of antibiotic resistance strains, there is an essential need to develop novel drug targets to address the challenge of multidrug-resistant bacteria. In current study, the idea was to utilize the available genome or proteome in a subtractive genome analyses protocol to identify drug targets within two of the MRSA types i.e., MRSA ST398 and MRSA 252. Recently, the use of subtractive genomic approaches helped in the identification and characterization of novel drug targets of a number of pathogens. Our protocol involved a similarity search between pathogen and host, essentiality study using the database of essential genes, metabolic functional association study using Kyoto Encyclopedia of Genes and Genomes database (KEGG), cellular membrane localization analysis and drug bank database. Functional family characterizations of the identified non homologous hypothetical essential proteins were done by SVMProt server. Druggability potential of each of the identified drug targets was also evaluated by Drug Bank database. Moreover, metabolic pathway analysis of the identified druggable essential proteins with KEGG revealed that the identified proteins are participating in unique and essential metabolic pathways amongst MRSA strains. In short, the complete proteome analyses by the use of advanced computational tools, databases and servers resulted in identification and characterization of few nonhomologous/hypothetical and essential proteins which are not homologous to the host genome. Therefore, these non-homologous essential targets ensure the survival of the pathogen and hence can be targeted for drug discovery.
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      PubDate: 2013-12-07T22:18:47Z
  • The Intrinsic dynamics of Cse1p and Xpot elucidated by coarse-grained
    • Abstract: Publication date: Available online 28 November 2013
      Source:Computational Biology and Chemistry
      Author(s): Ming-Wen Hu , Chiung-Fang Hsu , Byung Kim
      Cselp and Xopt are two karypherin proteins that transport the corresponding cargos during the nucleocytoplasmic transport. We utilized Elastic Network Model (ENM) and Finite Element Analysis (FEA) to study their conformational dynamics. These dynamics were interpreted by their intrinsic modes that played key roles in the flexibility of karyopherins, which further affected the binding affinities. The findings included that it was the karyopherin's versatile conformations composed of the same superhelices of HEAT repeats that produced different degrees of functional flexibilities. We presented evidence that these coarse-grained methods could help to elucidate the biological function behind the structures of the two karypherins.
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      PubDate: 2013-11-28T17:05:27Z
  • Multiscale modelling to understand the self-assembly mechanism of human
           β2-adrenergic receptor in lipid bilayer
    • Abstract: Publication date: Available online 16 November 2013
      Source:Computational Biology and Chemistry
      Author(s): Anirban Ghosh , Uddhavesh Sonavane , Rajendra Joshi
      The long perceived notion that G-Protein Coupled Receptors (GPCRs) function in monomeric form has recently been changed by the description of a number of GPCRs that are found in oligomeric states. The mechanism of GPCR oligomerization, and its effect on receptor function, is not well understood. In the present study, coarse grained molecular dynamics (CGMD) approach was adopted for studying the self-assembly process of the human GPCR, β2-adrenergic receptor (β2-AR), for which several experimental evidences of the dimerization process and its effect on cellular functions are available. Since the crystal structure of β2-AR lacks the third intracellular loop, initially it was modelled and simulated using restrained MD in order to get a stable starting conformation. This structure was then converted to CG representation and 16 copies of it, inserted into a hydrated lipid bilayer, were simulated for 10μs using the MARTINI force field. At the end of 10μs, oligomers of β2-AR were found to be formed through the self-assembly mechanism which were further validated through various analyses of the receptors. The lipid bilayer analysis also helped to quantify this assembly mechanism. In order to identify the domains which are responsible for this oligomerization, a reverse transformation of the CG system back to all-atom structure and simulated annealing run were carried out at the end of 10μs CGMD run. Analysis of the all-atom dimers thus obtained, revealed that TM1/TM1, H8/H8, TM1/TM5 and TM6/TM6 regions formed most of the dimerization surfaces, which is in accordance with some of the experimental observations and recent simulation results.
      Graphical abstract image

      PubDate: 2013-11-16T17:23:40Z
  • Computational simulation of ligand docking to L-type pyruvate kinase
    • Abstract: Publication date: Available online 8 November 2013
      Source:Computational Biology and Chemistry
      Author(s): Aleksei Kuznetsov , Ilona Faustova , Jaak Järv
      Computational blind docking approach was used for mapping of possible binding sites in L-type pyruvate kinase subunit for peptides, RRASVA and the phosphorylated derivative RRAS(Pi)VA, which model the phosphorylatable N-terminal regulatory domain of the enzyme. In parallel, the same docking analysis was done for both substrates of this enzyme, phosphoenolpyruvate (PEP) and adenosine diphosphate (ADP), and for docking of fructose 1,6-bisphosphate (FBP), which is the allosteric activator of the enzyme. The binding properties of the entire surface of the protein were scanned and several possible binding sites were identified in domains A and C of the protein, while domain B revealed no docking sites for peptides or for substrates or the allosteric regulator. It was found that the docking sites of different ligands were partially overlapping, pointing to the possibility that some regulatory effects, observed in the case of L-type pyruvate kinase, may be caused by the competition of different ligands for the same binding sites.
      Graphical abstract image

      PubDate: 2013-11-10T22:15:15Z
  • The Optimization of Running Time for a Maximum Common Substructure-Based
           Algorithm and Its Application in Drug Design
    • Abstract: Publication date: Available online 7 November 2013
      Source:Computational Biology and Chemistry
      Author(s): Jian Chen , Jia Sheng , Dijing Lv , Yang Zhong , Guoqing Zhang , Peng Nan
      In the field of drug discovery, it is particularly important to discover bioactive compounds through high-throughput virtual screening. The Maximum Common Substructure-based (MCS) algorithm is a promising method for the virtual screening of drug candidates. However, in practical applications, there is always a trade-off between efficiency and accuracy. In this paper, we optimized this method by running time evaluation using essential drugs defined by WHO and FDA-approved small-molecule drugs. The amount of running time allocated to the MCS-based virtual screening was varied, and statistical analysis was conducted to study the impact of computation running time on the screening results. It was determined that the running time efficiency can be improved without compromising accuracy by setting proper running time thresholds. In addition, the similarity of compound structures and its relevance to biological activity are analyzed quantitatively, which highlight the applicability of the MCS-based methods in predicting functions of small molecules. 15s to 30s was established as a reasonable range for selecting a candidate running time threshold. The effect of CPU speed is considered and the conclusion is generalized. The potential biological activity of small molecules with unknown functions can be predicted by the MCS-based methods
      Graphical abstract image

      PubDate: 2013-11-07T22:17:22Z
  • Targeting the Akt1 allosteric site to identify novel scaffolds through
           virtual screening
    • Abstract: Publication date: Available online 29 October 2013
      Source:Computational Biology and Chemistry
      Author(s): Oya Gursoy Yilmaz , Elif Ozkirimli Olmez , Kutlu O. Ulgen
      Preclinical data and tumor specimen studies report that AKT kinases are related to many human cancers. Therefore, identification and development of small molecule inhibitors targeting AKT and its signaling pathway can be therapeutic in treatment of cancer. Numerous studies report inhibitors that target the the ATP-binding pocket in the kinase domains, but the similarity of this site, within the kinase family makes selectivity a major problem. The sequence identity amongst PH domains is significantly lower than that in kinase domains and developing more selective inhibitors is possible if PH domain is targeted. This in silico screening study is the first time report toward the identification of potential allosteric inhibitors expected to bind the cavity between kinase and PH domains of Akt1. Structural information of Akt1 was used to develop structure-based pharmacophore models comprising hydrophobic, acceptor, donor and ring features. The 3D structural information of previously identified allosteric Akt inhibitors obtained from literature was employed to develop a ligand-based pharmacophore model. Database was generated with drug like subset of ZINC and screening was performed based on 3D similarity to the selected pharmacophore hypotheses. Binding modes and affinities of the ligands were predicted by Glide software. Top scoring hits were further analyzed considering 2D similarity between the compounds, interactions with Akt1, fitness to pharmacophore models, ADME, druglikeness criteria and Induced-Fit docking. Using virtual screening methodologies, derivatives of 3-methyl-xanthine, quinoline-4-carboxamide and 2-[4-(cyclohexa-1,3-dien-1-yl)-1H-pyrazol-3-yl]phenol were proposed as potential leads for allosteric inhibiton of Akt1.
      Graphical abstract image

      PubDate: 2013-11-01T22:16:48Z
  • Modeling of Tumor Growth in Dendritic Cell-based Immunotherapy Using
           Artificial Neural Networks
    • Abstract: Publication date: Available online 29 October 2013
      Source:Computational Biology and Chemistry
      Author(s): Mohammad Mehrian , Davud Asemani , Abazar Arabameri , Arash Pourgholaminejad , Jamshid Hadjati
      Exposure-response Modeling and Simulation is especially useful in oncology as it permits to predict and design un-experimented clinical trials as well as dose selection. Dendritic Cells (DC) are the most effective immune cells in the regulation of immune system. To activate immune system, DCs may be matured by many factors like bacterial CpG-DNA, Lipopolysaccharaide (LPS) and other microbial products In this paper, a model based on Artificial Neural Network (ANN) is presented for analyzing the dynamics of antitumor vaccines using empirical data obtained from the experimentations of different groups of mice treated with DCs matured by bacterial CpG-DNA, LPS and whole lysate of a Gram-positive bacteria Listeria monocytogenes. Also, tumor lysate was added to DCs followed by addition of maturation factors. Simulations show that the proposed model can interpret the important features of empirical data. Owing to the nonlinearity properties, the proposed ANN model has been able not only to describe the contradictory empirical results, but also to predict new vaccination patterns for controlling the tumor growth. For example, the proposed model predicts an exponentially-increasing pattern of CpG-matured DC to be effective in suppressing the tumor growth
      Graphical abstract image

      PubDate: 2013-10-29T17:22:57Z
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