title: In silico study on indole derivatives as anti HIV-1 agents: a combined docking, molecular dynamics and 3D-QSAR study.
abstract: 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.
authors: Department of Bio-New Drug Development, College of Medicine, Chosun University, 375 Seosuk-dong, Dong-gu, Gwangju, 501-759, Republic of Korea.
authors: Anand
authors: A
authors: Balupuri
authors: Changdev G
authors: CG
authors: Gadhe
authors: Pavithra K
authors: PK
authors: Balasubramanian
authors: Gugan
authors: G
authors: Kothandan
authors: Seung Joo
authors: SJ
authors: Cho
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects*; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology*; D016018:Least-Squares Analysis; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D015699:HIV Envelope Protein gp120; D007211:Indoles; C514793:gp120 protein, Human immunodeficiency virus 1