Int. J. Comput. Biol. Drug Des.最新文献

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Distance based knowledge retrieval through rule mining for complex biomarker recognition from tri-omics profiles 基于规则挖掘的基于距离的知识检索,用于三组学图谱中复杂生物标志物的识别
Int. J. Comput. Biol. Drug Des. Pub Date : 2019-05-11 DOI: 10.1504/IJCBDD.2019.10021269
Saurav Mallik, Zhongming Zhao
{"title":"Distance based knowledge retrieval through rule mining for complex biomarker recognition from tri-omics profiles","authors":"Saurav Mallik, Zhongming Zhao","doi":"10.1504/IJCBDD.2019.10021269","DOIUrl":"https://doi.org/10.1504/IJCBDD.2019.10021269","url":null,"abstract":"Biomarker discovery from complex biomedical data has become an important topic to unveil the significant new disease signals for disease diagnosis and treatment during past two decades. The earlier methods were proposed on a single genomic profile, and most of them utilize a single minimum support/confidence/lift cutoff. To overcome these shortcomings, here, we developed a framework for identifying complex markers using shortest distance based rule mining from the tri-omics profiles (gene expression, methylation and protein-protein interaction). We applied our method to a high-grade soft-tissue sarcomas multi-omics dataset. The novel markers were {GRB2-, STAT3-}('-' and '+' denote decreased and increased gene activities, respectively), {STAT3+, TP53-, MAPK3+} and {STAT3+, FYN+, MAPK3+}. We showed the superiority of our method vs. others, as it generates fewer rules and lower mean of the shortest distance than others. Moreover, our method is useful to extract complex markers from tri-omics profiles for the complex disease.","PeriodicalId":13612,"journal":{"name":"Int. J. Comput. Biol. Drug Des.","volume":"12 1","pages":"105-127"},"PeriodicalIF":0.0,"publicationDate":"2019-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87157677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Flexible molecular docking: application of hybrid tabu-simplex optimisation 柔性分子对接:混合禁忌-单纯形优化的应用
Int. J. Comput. Biol. Drug Des. Pub Date : 2019-03-07 DOI: 10.1504/IJCBDD.2019.098178
G. Khensous, B. Messabih, Abdallah Chouarfia, B. Maigret
{"title":"Flexible molecular docking: application of hybrid tabu-simplex optimisation","authors":"G. Khensous, B. Messabih, Abdallah Chouarfia, B. Maigret","doi":"10.1504/IJCBDD.2019.098178","DOIUrl":"https://doi.org/10.1504/IJCBDD.2019.098178","url":null,"abstract":"In this paper, we present a molecular docking method to predict the optimal binding pose of a flexible ligand in a flexible protein-binding pocket. For this purpose, a Tabu global search optimization algorithm is used, and the best Tabu solutions are then refined using the Nelder-Mead Simplex local search optimization algorithm. Most docking methods use scoring functions to approximate the binding affinity between the two molecular partners. In our application, the intra-molecular and intermolecular energies are calculated explicitly from a classical molecular mechanics model, which includes polarization terms. The variables of our optimization problem are the ligand positions (Euler angles + translation vector), the ligand and the protein side chains dihedral angles instead of the Cartesian coordinates in order to reduce the problem dimensionality. While the GOLD software (GOLD for Genetic Optimization for Ligand Docking) is usually considered as a standard in molecular docking, our docking approach is illustrated on four protein/ligand complexes for which GOLD failed, suggesting that the proposed method is promising.","PeriodicalId":13612,"journal":{"name":"Int. J. Comput. Biol. Drug Des.","volume":"1 1","pages":"34-53"},"PeriodicalIF":0.0,"publicationDate":"2019-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82254767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Protein interaction network analysis of TGF-β signalling pathway enabled EMT process to anticipate the anticancer activity of curcumin TGF-β信号通路的蛋白相互作用网络分析使EMT过程能够预测姜黄素的抗癌活性
Int. J. Comput. Biol. Drug Des. Pub Date : 2019-03-07 DOI: 10.1504/IJCBDD.2019.098183
Shivananda Kandagalla, S. Shekarappa, Bharath Basavapattana Rudresh, Pavan Gollapalli, M. Hanumanthappa
{"title":"Protein interaction network analysis of TGF-β signalling pathway enabled EMT process to anticipate the anticancer activity of curcumin","authors":"Shivananda Kandagalla, S. Shekarappa, Bharath Basavapattana Rudresh, Pavan Gollapalli, M. Hanumanthappa","doi":"10.1504/IJCBDD.2019.098183","DOIUrl":"https://doi.org/10.1504/IJCBDD.2019.098183","url":null,"abstract":"TGF-β signalling is a key mediator of epithelial to mesenchymal transition (EMT) process and its up-regulation is identified as a hallmark of metastasis. Since TGF-β signalling pathway is known as a key therapeutic target in the treatment of EMT enabled cancer and the study aims at identification of key EMT genes by gene annotation tools and protein interaction network (PIN) to analyse the regulatory dynamics of an interactome. Meanwhile, the potency of curcumin against TGF-β signalling was evaluated by network pharmacology approach. Resultantly, 15 genes were identified as key regulators of TGF-β signalling pathway and seven were shortlisted as leading curcumin targets. Cumulatively, both approaches have justified the role of targets. Thus, curcumin was subjected to molecular docking with targets using AutoDock Vina. Wherein, curcumin has shown significant binding energy with targets EP300 and JUN (-7.1 and -6.4 kcal/mol) respectively indicating the potential anticancer property.","PeriodicalId":13612,"journal":{"name":"Int. J. Comput. Biol. Drug Des.","volume":"32 1","pages":"54-79"},"PeriodicalIF":0.0,"publicationDate":"2019-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85040203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
In-silico mutational study of ferulic acid decarboxylase for improvement of substrate binding empathy 阿魏酸脱羧酶改善底物结合移情的硅基突变研究
Int. J. Comput. Biol. Drug Des. Pub Date : 2019-03-07 DOI: 10.1504/IJCBDD.2019.098177
Pravin Kumar, Shashwati Ghosh Sachan, R. Poddar
{"title":"In-silico mutational study of ferulic acid decarboxylase for improvement of substrate binding empathy","authors":"Pravin Kumar, Shashwati Ghosh Sachan, R. Poddar","doi":"10.1504/IJCBDD.2019.098177","DOIUrl":"https://doi.org/10.1504/IJCBDD.2019.098177","url":null,"abstract":"Biotransformation of ferulic acid by microorganisms provides a better alternative for production of flavour and fragrance compounds like 4-vinylguaiacol and vanillin. Ferulic acid is transformed to 4-vinylguaiacol using the non-oxidative decarboxylation pathway by ferulic acid decarboxylase (FADase). Here we report, computational mutational analysis of active site of FADase. Site directed mutations (single nucleotide polymorphisms, SNPs) were commenced using in-silico molecular modelling methods. Energy minimisation, dynamic cross-correlation map (DCCM) and principle components analysis (PCA) methods were subsequently applied to validate different conformers (SNPs) of FADase. Substrate ferulic acid was docked with different SNPs. It was observed that, certain amino acids like Tyr21, Trp25, Tyr27 and Glu134 at active sites are responsible for better binding to ferulic acid. Further, mutated form Y27F (Tyr27Phe) of FADase shows a better binding affinity towards ferulic acid than its native form through structure analysis and docking studies.","PeriodicalId":13612,"journal":{"name":"Int. J. Comput. Biol. Drug Des.","volume":"41 1","pages":"16-33"},"PeriodicalIF":0.0,"publicationDate":"2019-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76238915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Interaction studies of Angelica polymorpha and Beilschmiedia pulverulenta phytochemicals with acetylcholinesterase as anti-Alzheimer's disease target 当归、白芷与抗阿尔茨海默病靶点乙酰胆碱酯酶的相互作用研究
Int. J. Comput. Biol. Drug Des. Pub Date : 2019-03-07 DOI: 10.1504/IJCBDD.2019.098180
T. H. Ogunwa
{"title":"Interaction studies of Angelica polymorpha and Beilschmiedia pulverulenta phytochemicals with acetylcholinesterase as anti-Alzheimer's disease target","authors":"T. H. Ogunwa","doi":"10.1504/IJCBDD.2019.098180","DOIUrl":"https://doi.org/10.1504/IJCBDD.2019.098180","url":null,"abstract":"Angelica polymorpha and Beilschmiedia pulverulenta are medicinal plants locally used by people in some parts of Asia and Africa due to their beneficial health effects particularly in the treatment of Alzheimer's disease (AD). The phytoconstituents responsible for such bioactivity have recently been identified in the plants. Herein, in silico approach was used to explore the interaction of such phytochemicals with acetylcholinesterase (AChE) as a validated target in the treatment of AD to provide insights into their precise binding pattern and affinity, order of chemical interaction, inhibitory potential and residues that contribute to the enzyme-phytoconstituent complex stability. With binding affinity ranging from -7.0 kcal/mol to -10.2 kcal/mol and tacrine-comparable orientation, the chemical scaffold of the phytochemicals from both plants displayed deep penetration and fit conveniently into the narrow gorge of AChE. Optimisation of these ligands scaffold might yield new AChE inhibitors with desirable higher efficacy.","PeriodicalId":13612,"journal":{"name":"Int. J. Comput. Biol. Drug Des.","volume":"1 1","pages":"80-99"},"PeriodicalIF":0.0,"publicationDate":"2019-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88314887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Development of specific DHODH inhibitors for Plasmodium and Human species 疟原虫和人类特异性DHODH抑制剂的研制
Int. J. Comput. Biol. Drug Des. Pub Date : 2019-03-07 DOI: 10.1504/IJCBDD.2019.098175
P. Swaminathan, L. Saleena
{"title":"Development of specific DHODH inhibitors for Plasmodium and Human species","authors":"P. Swaminathan, L. Saleena","doi":"10.1504/IJCBDD.2019.098175","DOIUrl":"https://doi.org/10.1504/IJCBDD.2019.098175","url":null,"abstract":"Malaria still remains one of the challenging public health issue infecting about 300-500 millions of people. The most serious and fatal malarial infections are caused by Plasmodium falciparum which has developed resistance to commonly employed therapeutics. Hence the need to develop a novel anti-malarial drug targeting Dihydroorotate dehydrogenase (DHODH), an enzyme involved in parasite growth. DHODH is present in both humans and Plasmodium falciparum. Sequence analysis and structure comparison of DHODH of both Human and Plasmodium falciparum reveals variations among them, thereby providing a chance to design a specific inhibitor. Virtual screening of existing anti-malarial drugs acting on DHODH is performed from Pubchem and BindingDB databases. Pharmacophore mapping was done for the top 20 virtual screening compounds using hip hop algorithm. The compounds thus obtained from screening, are docked with both Human and Plasmodium DHODH. Potential anti-malarial lead compounds can be developed to treat resistant strains of Plasmodium falciparum.","PeriodicalId":13612,"journal":{"name":"Int. J. Comput. Biol. Drug Des.","volume":"18 1","pages":"1-15"},"PeriodicalIF":0.0,"publicationDate":"2019-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74803911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Simulating genetically heterozygous genomes in the tumour tissue according to its clonal evolution history 根据肿瘤组织的克隆进化历史模拟肿瘤组织的遗传杂合基因组
Int. J. Comput. Biol. Drug Des. Pub Date : 2019-01-01 DOI: 10.1504/IJCBDD.2019.10021272
Yan-Shuo Chu, Mingxiang Teng, Yadong Wang
{"title":"Simulating genetically heterozygous genomes in the tumour tissue according to its clonal evolution history","authors":"Yan-Shuo Chu, Mingxiang Teng, Yadong Wang","doi":"10.1504/IJCBDD.2019.10021272","DOIUrl":"https://doi.org/10.1504/IJCBDD.2019.10021272","url":null,"abstract":"","PeriodicalId":13612,"journal":{"name":"Int. J. Comput. Biol. Drug Des.","volume":"150 1","pages":"143-152"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84977108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploration of cyclooxygenase-1 binding modes of some chiral anti-inflammatory drugs using molecular docking and dynamic simulations 基于分子对接和动态模拟的手性抗炎药环氧化酶-1结合模式研究
Int. J. Comput. Biol. Drug Des. Pub Date : 2019-01-01 DOI: 10.1504/ijcbdd.2019.10022513
Meriem Meyar, S. Feddal, Zohra Bouakouk, S. Kellou-Tairi
{"title":"Exploration of cyclooxygenase-1 binding modes of some chiral anti-inflammatory drugs using molecular docking and dynamic simulations","authors":"Meriem Meyar, S. Feddal, Zohra Bouakouk, S. Kellou-Tairi","doi":"10.1504/ijcbdd.2019.10022513","DOIUrl":"https://doi.org/10.1504/ijcbdd.2019.10022513","url":null,"abstract":"","PeriodicalId":13612,"journal":{"name":"Int. J. Comput. Biol. Drug Des.","volume":"10 1","pages":"281-301"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74292555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring polypharmacology of some natural products using similarity search target fishing approach 利用相似搜索靶标垂钓法探索一些天然产物的多药理学
Int. J. Comput. Biol. Drug Des. Pub Date : 2018-11-14 DOI: 10.1504/IJCBDD.2018.096126
I. Almasri
{"title":"Exploring polypharmacology of some natural products using similarity search target fishing approach","authors":"I. Almasri","doi":"10.1504/IJCBDD.2018.096126","DOIUrl":"https://doi.org/10.1504/IJCBDD.2018.096126","url":null,"abstract":"Natural products have long been considered as important sources for drug discovery due to the diversity of their chemical structures and broad range of biological activities attained by modulation of different biological targets. Therefore, the identification of the molecular targets of natural products is a milestone step in rational design of more potent and safer compounds. In this work, we explored the polypharmacology of three natural products having pleiotropic health beneficial effects: resveratrol, curcumin and berberine, using a ligand-based target fishing approach. The fishing protocol was started with the generation of a chemogenomic database that links individual targets with specific target ligands or group of drugs. Targets profile was then generated using ROCS software. The applied method was able not only to retrieve known targets within the top-ranked list for the natural compounds but also identified off-targets which were found by docking simulation to be potential targets and were consistent with recently identified bioactivities of these compounds.","PeriodicalId":13612,"journal":{"name":"Int. J. Comput. Biol. Drug Des.","volume":"28 1","pages":"295-309"},"PeriodicalIF":0.0,"publicationDate":"2018-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81713908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A genetic programming-based approach and machine learning approaches to the classification of multiclass anti-malarial datasets 基于遗传规划和机器学习的多类抗疟疾数据集分类方法
Int. J. Comput. Biol. Drug Des. Pub Date : 2018-11-14 DOI: 10.1504/IJCBDD.2018.096125
Madhulata Kumari, Neeraj Tiwari, N. Subbarao
{"title":"A genetic programming-based approach and machine learning approaches to the classification of multiclass anti-malarial datasets","authors":"Madhulata Kumari, Neeraj Tiwari, N. Subbarao","doi":"10.1504/IJCBDD.2018.096125","DOIUrl":"https://doi.org/10.1504/IJCBDD.2018.096125","url":null,"abstract":"Feature selection approaches have been widely applied to deal with the various sample size problem in the classification of activity of datasets. The present work focuses on the understanding system of descriptors of anti-malarial inhibitors by Genetic programming (GP) to understand the impact of descriptors on inhibitory effects. The experimental dataset of inhibitors of anti-malarial was used to derive the optimised system by GP. Additionally, we have developed machine learning models using the random forest, decision tree, support vector machine (SVM) and Naive Bayes on an antimalarial dataset obtained from ChEMBL database and evaluated for their predictive capability. Based on the statistical evaluation, Random Forest model showed the higher area under the curve (AUC), better accuracy, sensitivity, and specificity in the cross-validation tests as compared to others. The statistical results indicated that the RF model was the best predictive model with 82.51% accuracy, 89.7% ROC. We deployed the RF classifier model on three datasets; phytochemical compound dataset, NCI natural product dataset IV and approved drugs dataset containing 918, 423 and 1554 compounds resulting 153, 81 and 250 compounds respectively as anti-malarial compounds. Further, to prioritise drug-like compounds, Lipinski's rule was applied on active phytochemicals which resulted in 13 hit anti-malarial molecules. Thus, such predictive models are useful to find out novel hit anti-malarial compounds and could also be used to discover novel drugs for other diseases.","PeriodicalId":13612,"journal":{"name":"Int. J. Comput. Biol. Drug Des.","volume":"46 1","pages":"275-294"},"PeriodicalIF":0.0,"publicationDate":"2018-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88961147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
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