title: Structural and energetic analyses of the effects of the K103N mutation of HIV-1 reverse transcriptase on efavirenz analogues.
abstract: The effect of the K103N mutation of HIV-1 reverse transcriptase (RT) on the activity of efavirenz analogues was studied via Monte Carlo/free energy perturbation calculations. The relative fold resistance energies indicate that efavirenz binds to K103N RT in a manner similar to the wild-type enzyme. The improved performance of the quinazolinones against the mutant enzyme is attributed to formation of a more optimal hydrogen-bonding network with bridging water molecules between the ligands and Glu138.
authors.affiliation: Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Udier-Blagović
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; D003521:Cyclopropanes; D054303:HIV Reverse Transcriptase / Q000737:chemistry* / Q000235:genetics*; D008958:Models, Molecular; D009010:Monte Carlo Method; D009154:Mutation; D010078:Oxazines / Q000737:chemistry*; D011485:Protein Binding; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D010078:Oxazines; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; C098320:efavirenz