In silico study on indole derivatives as anti HIV-1 agents: a combined docking, molecular dynamics and 3D-QSAR study

Balupuri, Anand; Gadhe, Changdev G.; Balasubramanian, Pavithra K.; Kothandan, Gugan; Cho, Seung Joo

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자료유형: 학술저널

저자정보: Balupuri, Anand (Department of Bio-New Drug Development, College of Medicine, Chosun University) Gadhe, Changdev G. (Department of Bio-New Drug Development, College of Medicine, Chosun University) Balasubramanian, Pavithra K. (Department of Bio-New Drug Development, College of Medicine, Chosun University) Kothandan, Gugan (Department of Bio-New Drug Development, College of Medicine, Chosun University) Cho, Seung Joo (Department of Bio-New Drug Development, College of Medicine, Chosun University)

저널정보: 대한약학회 Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea 제37권 제8호

발행연도: 2014.1

수록면: 1,001 - 1,015 (15page)

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The HIV-1 envelope glycoprotein gp120 plays a vital role in the entry of virus into the host cells and is a potential antiviral drug target. Recently, indole derivatives have been reported to inhibit HIV-1 through binding to gp120, and this prevents gp120 and CD4 interaction to inhibit the infectivity of HIV-1. In this work, molecular docking, molecular dynamics (MD) and three-dimensional quantitative structure-activity relationship studies were carried out. Molecular docking studies of the most active and the least active compounds were performed to identify important residues in the binding pocket. We refined the docked poses by MD simulations which resulted in conformational changes. After equilibration, the structure of the ligand and receptor complex was stable. Therefore, we just took the last snapshot as the representative binding pose for this study. This pose for the most active inhibitor was used as a template for receptor-based alignment which was subsequently used for comparative molecular field analysis. Resultant 3D contour maps suggested smaller substituents are desirable at the 7-position of indole ring to avoid steric interactions with Ser375, Phe382 and Tyr384 residues in the active site. These results can be exploited to develop potential leads and for structure-based drug design of novel HIV-1 inhibitors.

#HIV-1 entry inhibitors #gp120 #CoMFA #Molecular docking #Molecular dynamics simulation #MM-GBSA

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