Docking and quantitative structure-activity relationship studies for the bisphenylbenzimidazole family of non-nucleoside inhibitors of HIV-1 reverse transcriptase.
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.
Lagos
Carlos F
CF
Centre for Bioinformatics CBUC, Faculty of Biological Sciences, Pontificia Universidad Catolica de Chile, Portugal 49-Zocalo, Santiago 6513492, Chile. carlos@cbuc.cl
Caballero
Julio
J
Gonzalez-Nilo
Fernando D
FD
David Pessoa-Mahana
Carlos
C
Perez-Acle
Tomas
T
D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D003198:Computer Simulation; D015195:Drug Design; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D017434:Protein Structure, Tertiary; D021281:Quantitative Structure-Activity Relationship; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry* / Q000494:pharmacology
D001562:Benzimidazoles; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase