شناسایی مهار کننده های جدید سیکلو اکسیژناز-2 با استفاده از روش غربالگری مجازی ساختاری و شبیه سازی دینامیک مولکولی

رزاقی اصل, نیما and میرزایی, سحر and مهنام, کریم and سپهری, ساقی (1397) شناسایی مهار کننده های جدید سیکلو اکسیژناز-2 با استفاده از روش غربالگری مجازی ساختاری و شبیه سازی دینامیک مولکولی. Journal of Molecular Graphics and Modelling ــ 83 . pp. 138-152. شاپا 1093-3263

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Identification of COX-2 inhibitors via structure-based virtual screening and molecular dynamics simulation

English Abstract

In an attempt to identify potential COX-2 inhibitors, a multi-step virtual screening strategy was performed on a series of compounds. For this purpose, ZINC database was screened on the basis of 50% structural similarity with celecoxib and indomethacin as the representative of COX-2 and COX-1/COX-2 inhibitors, respectively. Selected molecules were subjected to various filters such as Lipinski's rule of five and also several ADME parameters. Toxicity risk of molecules was approximated via in silico methods. Moreover, COX-2 inhibitory activities of the selected compounds were predicted using PASS program. Molecular docking was performed to improve the accuracy of screening and also to find the details of the interactions of the hit compounds with the active site. Finally, MD simulations on top-ranked structures ZINC_1130464, ZINC_3181760, ZINC_33402495 and celecoxib were carried out with COX-2. Furthermore, RMSD, RMSF, hydrogen binds, Rg and energy analysis during MD simulation certainly indicated the stable binding of selected compounds with COX-2 structure. Moreover, docking and MD results revealed that hydrophobic contacts and optimum hydrogen bonds were determinant factors in the interactions of in silico hits and COX-2.

Item Type:Article
زبان سند : انگلیسی
نویسنده اول :نیما رزاقی اصل
نویسنده :سحر میرزایی
نویسنده :کریم مهنام
نویسنده مسئول :ساقی سپهری
Additional Information:Impact Factor (2017) 1.885 Indexed in: ISI, Pubmed/Medline/Index Medicus, Scopus, Chemical Abstracts, Current Contents, Scisearch, Elsevier BIOBASE, Computer and Information Systems Abstracts Journal
کلیدواژه ها (انگلیسی):COX2 INHIBITOR - Virtual screening - Molecular dynamics
Subjects:QV pharmacology > QV 744 Medicinal Chemistry
Divisions:School of Pharmacy > Department of Medicinal Chemistry
ID Code:10190
Deposited By: Dr Nima Razzaghi-Asl
Deposited On:06 Apr 1397 12:34
Last Modified:06 Apr 1397 12:34

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