Docking and Quantitative Structure-Activity Relationship Studies for the Bisphenylbenzimidazole Family of Non-Nucleoside Inhibitors of HIV-1 Reverse Transcriptase

作者：Lagos Carlos F^*; Caballero Julio; Gonzalez Nilo Fernando D; Pessoa Mahana Carlos David; Perez Acle Tomas

来源：Chemical Biology & Drug Design, 2008, 72(5): 360-369.

DOI：10.1111/j.1747-0285.2008.00716.x

• bisphenylbenzimidazole derivatives
• docking
• non-nucleoside HIV-1 reverse transcriptase inhibitors
• quantitative structure-activity relationship
• radial distribution function descriptors

Molecular docking studies on a set of bisphenylbenzimidazole derivatives were conducted to identify the compounds binding orientations within the HIV-1 reverse transcriptase non-nucleoside binding pocket. A good correlation between the calculated binding free energies and the experimental inhibitory activities suggests that the identified binding conformations of these inhibitors are reliable. Based on obtained bisphenylbenzimidazoles binding conformations, a predictive quantitative structure-activity relationship model based on radial distribution function descriptors was developed. The obtained quantitative structure-activity relationship model was predictive according to internal and external validation experiments and might provide guidelines for the design of novel non-nucleoside HIV-1 reverse transcriptase inhibitors based on the 1-benzyl-2-arylbenzimidazole scaffold.

• 出版日期2008-11
• 单位上海生物信息技术研究中心