Molecular Docking and 3D-QSAR Research of Diaryltriazines Derivatives as HIV-1 Reverse Transcriptase Inhibitors

• 1、Key Laboratory of Biorheological Science and Technology (Ministry of Education), Chongqing University
• 2、College of Bioengineering, Chongqing University

Abstract：The molecular docking followed by comparative molecular similarity index analysis (CoMSIA) was employed to the three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of HIV-1 reverse transcriptase inhibitory activity of 40 diaryltriazines derivatives. The results showed that hydrophobic interactions between bottom of the receptor and two aromatic rings of ligands, electrostatic interactions between receptor and the triazine ring and R4 substituent, and the steric hindrance between the receptor and R4 substituent were the dominant factors affecting the binding affinities. Based on the docking conformations, CoMSIA were employed to the QSAR studies of 40 diaryltriazines derivatives. The number of principal components, r2, q2 (leave-one-out, LOO), r2pred of the optimal CoMSIA model were 6, 0.971, 0.738 and 0.833 respectively. Based on the results of docking and CoMSIA models, two solutions to optimize diaryltriazines derivatives were put forward: one solution was aimed to enhance the effect of hydrophobic interactions and steric complementation, the other was aimed to increase the electrostatic interactions between the receptor and R4 substituent, and, at the same time, avoid the steric effect of R4 substituent.

Keywords： three-dimensional quantitative structure-activity relationship comparative molecular similarity index analysis molecular docking Diaryltriazines Derivatives reverse transcriptase Inhibitors