title: Activity predictions for efavirenz analogues with the K103N mutant of HIV reverse transcriptase.
abstract: 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.
authors.affiliation: Department of Chemistry, Yale University, New Haven, CT 06520-8107, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Udier-Blagović
authors.forename: Edward K
authors.initials: EK
authors.lastname: Watkins
authors.forename: Julian
authors.initials: J
authors.lastname: Tirado-Rives
authors.forename: William L
authors.initials: WL
authors.lastname: Jorgensen
mesh_terms: 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
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D010078:Oxazines; D054303:HIV Reverse Transcriptase; C098320:efavirenz