Activity predictions for efavirenz analogues with the K103N mutant of HIV reverse transcriptase

Monte Carlo-extended linear response (MC/ELR) calculations are used to examine the binding of efavirenz analogues with the K103N mutant of HIV-1 reverse transcriptase (HIVRT). A regression equation previously reported for the wild type (WT) enzyme is shown to predict 47 experimental activities for the K103N mutant with a q2=0.55 and avg error of only 0.46 kcal/mol. Further analysis identifies the key features for binding to the K103N mutant: ligand flexibility, burial of hydrophobic surface area, and protein–ligand van der Waals interactions.