روش سطح پاسخ در مطالعه داکینگ مولکولی ترکیبات غیرپپتیدی مهار کننده آنزیم بتا-سکرتاز

رزاقی اصل, نیما and میری, رامین and عبادی, احمد and ادراکی, نجمه and مهدی پور, احمد رضا and شهابی پور, سارا (1391) روش سطح پاسخ در مطالعه داکینگ مولکولی ترکیبات غیرپپتیدی مهار کننده آنزیم بتا-سکرتاز. Journal of Molecular Modeling ــ 18 (10). pp. 4567-4576. شاپا 1610-2940

Text - Published Version

Official URL: http://link.springer.com/article/10.1007%2Fs00894-...


Response surface methodology in docking study of small molecule BACE-1 inhibitors

English Abstract

Computational evaluation of ligand-receptor binding via docking strategy is a well established approach in structure-based drug design. This technique has been applied frequently in developing molecules of biological interest. However, any procedure would require an optimization set up to be more efficient, economic and time-saving. Advantages of modern statistical optimization methods over conventional one-factor-at-a-time studies have been well revealed. The optimization by experimental design provides a combination of factor levels simultaneously satisfying the requirements considered for each of the responses and factors. In this study, response surface method was applied to optimize the prominent factors (number of genetic algorithm runs, population size, maximum number of evaluations, torsion degrees for ligand and number of rotatable bonds in ligand) in AutoDock4.2-based binding study of small molecule β-secretase inhibitors as anti-alzheimer agents. Results revealed that a number of rotatable bonds in ligand and maximum number of docking evaluations were determinant variables affecting docking outputs. The interference between torsion degrees for ligand and number of genetic algorithm runs for docking procedure was found to be the significant interaction term in our model. Optimized docking outputs exhibited a high correlation with experimental fluorescence resonance energy transfer-based IC50s for β-secretase inhibitors (R2 = 0.9133).

Item Type:Article
زبان سند : انگلیسی
نویسنده اول :نیما رزاقی اصل
نویسنده مسئول :رامین میری
نویسنده :احمد عبادی
نویسنده :نجمه ادراکی
نویسنده :احمد رضا مهدی پور
نویسنده :سارا شهابی پور
Additional Information:2013 Impact Factor : 1.867 Abstracted/Indexed in : Science Citation Index Expanded (SciSearch), Journal Citation Reports/Science Edition, PubMed/Medline, SCOPUS, EMBASE, Chemical Abstracts Service (CAS), Google Scholar, EBSCO, CSA, CAB International, Academic OneFile, Academic Search, AGRICOLA, CAB Abstracts, CSA Environmental Sciences, Current Contents/ Life Sciences, Current Contents/Physical, Chemical and Earth Sciences, EMBiology, Gale, Global Health, OCLC, Referativnyi Zhurnal (VINITI), SCImago, Summon by ProQuest
Uncontrolled Keywords:آلزایمر، بتا-سکرتاز، سطح پاسخ، داکینگ، بهینه سازی
کلیدواژه ها (انگلیسی):Alzheimer , BACE-1 , Box-Behnken , Docking , Optimization
Subjects:QV pharmacology > QV 744 Medicinal Chemistry
Divisions:School of Pharmacy > Department of Medicinal Chemistry
ID Code:6073
Deposited By: Dr Nima Razzaghi-Asl
Deposited On:26 Aug 1393 05:36
Last Modified:26 Aug 1393 05:36

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