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 q(2)=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.
Udier-Blagović
Marina
M
Department of Chemistry, Yale University, New Haven, CT 06520-8107, USA.
Watkins
Edward K
EK
Tirado-Rives
Julian
J
Jorgensen
William L
WL
D000480:Alkynes; D048588:Benzoxazines; D001665:Binding Sites / Q000187:drug effects / Q000235:genetics; D003521:Cyclopropanes; D054303:HIV Reverse Transcriptase / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D010078:Oxazines / Q000737:chemistry* / Q000378:metabolism*; D011237:Predictive Value of Tests
D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D010078:Oxazines; D054303:HIV Reverse Transcriptase; C098320:efavirenz