Theoretical investigation of highly potent HIV-1 RT inhibitors in the class of efavirenz derivatives, based on quantum chemical calculations and molecular modeling

Comformational analysis of HIV-1 reverse transcriptase inhibitor (s)-6-chloro-4-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3, 1-benzoxazin-2-one (efavirenz) and selected derivatives were investigated based on various methods of quantum chemical calculations. The 2D PES and 3D PES for these compounds were examined. The results show that the conformational anlysis based on high theory of calculations could provide beneficial information concerning the preferred conformation. Moreover, the conformation analysis results are accurate enough to predict the binding mode of compounds comparable to docking calculations. Consecutively, molecular docking and 3D-QSAR analyses were performed to understand the interaction between a series of efavirenz derivatives with WT and K103N HIV-1 RT. To model the potential binding modes od efavirenz derivatives in the binding pocket of WT and K103N HIV-1 RT, molecular docking approach by using Autodock 3.05 program was carried out.