پیش بینی فعالیت ضد HIV-1 مهارکننده های جدید gp41 با استفاده از غربالگری مجازی بر اساس ساختار و شبیه سازی دینامیک مولکولی

سپهری, ساقی and سقایی, لطف الله and فصیحی, افشین (1396) پیش بینی فعالیت ضد HIV-1 مهارکننده های جدید gp41 با استفاده از غربالگری مجازی بر اساس ساختار و شبیه سازی دینامیک مولکولی. Molecular informatics ــ 36 (3). شاپا 1868-1743

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Official URL: https://onlinelibrary.wiley.com/doi/10.1002/minf.2...


Anti‐HIV‐1 Activity Prediction of Novel Gp41 Inhibitors Using Structure‐Based Virtual Screening and Molecular Dynamics Simulation

English Abstract

The fusion of viral and host cell membranes is mediated using gp41 subunit of the human immunodeficiency virus type 1 (HIV‐1) envelope glycoprotein. As the HIV‐1 enters the host cells, the two helical regions (HR1 and HR2) in the ectodomain of gp41 form a six‐helix bundle, which carries the target and viral cell membranes to close proximity. Steps of this process serve as attractive targets for developing HIV‐1 fusion inhibitors. Identification of some novel HIV fusion inhibitors with the goal of blocking the formation of the six‐helix bundle was accomplished by computer‐aided drug design techniques. A virtual screening strategy was employed to recognize small molecules presumably able to bind the gp41 at the internal interface of the NHR helices at the core native viral six‐helix. This study was carried out in two stages. In the first stage, a library of more than seven thousand compounds was collected from ZINC, PubChem and BindingDB databases and protein data bank. Key contacts of known inhibitors with gp41 binding site residues were considered as the collecting criteria. In the second stage series of filtering processes were performed on this library in subsequent steps to find the potential gp41 inhibitors. The filtering criteria included pharmacokinetic and ADMET properties as well as in silico anti‐HIV‐1 prediction. Molecular docking simulation was carried out to identify interactions of the filtered molecules with the key residues in the gp41 binding site. Finally, molecular dynamics simulation indicates the superior inhibitory ability of three selected compounds over the known gp41inhibitor, NB‐64.

Item Type:Article
زبان سند : انگلیسی
نویسنده اول :ساقی سپهری
نویسنده :لطف الله سقایی
نویسنده مسئول :افشین فصیحی
Additional Information:Impact Factor(2017) 1.955 Indexed in: ISI, Pubmed/Medline/Index Medicus, Scopus, Embase, Chemical Abstracts Service , Advanced Technologies & Aerospace Database, Agricultural & Environmental Science Database, BIOBASE: Current Awareness in Biological Sciences, Biological Abstracts
کلیدواژه ها (انگلیسی):virtual screening · molecular docking · PASS · gp41 · molecular dynamic
Subjects:QV pharmacology > QV 744 Medicinal Chemistry
Divisions:School of Pharmacy > Department of Medicinal Chemistry
ID Code:10724
Deposited By: ساقی سپهری
Deposited On:13 Aug 1397 18:24
Last Modified:13 Aug 1397 18:24

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