اثر کنفورماسیون بیومولکولی بر شبیه سازی داکینگ: مطالعه موردی بر روی یک مهار کننده پر قدرت آنزیم HIV-1 پروتئاز

رزاقی اصل, نیما and سپهری, ساقی and عبادی, احمد and شهابی پور, سارا and میری, رامین (1394) اثر کنفورماسیون بیومولکولی بر شبیه سازی داکینگ: مطالعه موردی بر روی یک مهار کننده پر قدرت آنزیم HIV-1 پروتئاز. Iranian Journal of Pharmaceutical Research ــ 14 (3). pp. 785-802. شاپا 0328-1735

Text - Published Version

Official URL: http://ijpr.sbmu.ac.ir/article_1674_75.html


Effect of Biomolecular Conformation on Docking Simulation: A Case Study on a Potent HIV-1 Protease Inhibitor

English Abstract

Human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) is a disease pertained to the human immune system. Given its crucial role in viral replication, HIV-1 protease (HIV-1 PR) is a prime therapeutic target in AIDS therapy. In this regard, the dynamic aspects of ligand-enzyme interactions may indicate an important role of conformational variability in HIV-1 PR inhibitor/drug design. In the present contribution, the effect of HIV-1 PR flexibility (within multiple crystallographic structures of HIV-1 PR) on binding to the Amprenavir was elucidated via an ensemble docking approach. Molecular docking studies were performed via advanced AutoDock4.2 software. Ensemble docking of Amprenavir into the active site of various conformations of HIV-1 PR predicted different interaction modes/energies. Analysis of binding factors in terms of docking false negatives/positives revealed a determinant role of enzyme conformational variation in prediction of optimum induced fit (PDB ID: 1HPV). The outcomes of this study demonstrated that conformation of receptor may significantly affect the accuracy of docking/binding results in structure-based rational design of anti HIV-1 PR agents. Furthermore; some strategies to re-score the docking results in HIV-1 PR targeted docking studies were proposed.

Item Type:Article
زبان سند : انگلیسی
نویسنده مسئول :نیما رزاقی اصل
نویسنده :ساقی سپهری
نویسنده :احمد عبادی
نویسنده :سارا شهابی پور
نویسنده :رامین میری
Additional Information:IF: 1.352 Indexed in: ISI, SCOPUS, PubMed/PMC
کلیدواژه ها (انگلیسی):AIDS, HIV-1 PR, Amprenavir, Docking
Subjects:QV pharmacology > QV 744 Medicinal Chemistry
Divisions:School of Pharmacy > Department of Medicinal Chemistry
ID Code:5375
Deposited By: Dr Nima Razzaghi-Asl
Deposited On:23 Apr 1394 03:48
Last Modified:11 Dec 1401 12:27

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