title: A study of the binding energies of efavirenz to wild-type and K103N/Y181C HIV-1 reverse transcriptase based on the ONIOM method.
abstract: A three-layered ONIOM model was used to study the interactions between efavirenz and the binding sites of HIV-1 reverse transcriptase (RT): wild-type and double mutant K103N/Y181C enzyme forms. Binding energies were determined and compared to describe the loss of activity of efavirenz with the mutant HIV-1 RT binding pocket. The calculated binding energy for the efavirenz-K103N/Y181C HIV-1 RT complex is less than that with the wild-type complex by approximately 8 kcal mol(-1). The interaction energies, calculated at the MP2/6-31G(d,p) level between efavirenz and individual residues surrounding the binding pocket of the K103N/Y181C enzyme, demonstrate that the attractive interactions between efavirenz and residue positions 101 and 103 were less than those for wild-type RT by 5.52 and 3.62 kcal mol(-1), respectively. Understanding these interactions could be useful in the design of inhibitors specific for the HIV-1 RT allosteric site and that have greater potency against the mutant enzyme.
authors.affiliation: Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand.
authors.forename: Pensri
authors.initials: P
authors.lastname: Srivab
authors.forename: Supa
authors.initials: S
authors.lastname: Hannongbua
mesh_terms: D000480:Alkynes; D048588:Benzoxazines / Q000737:chemistry*; D001665:Binding Sites; D003521:Cyclopropanes; D054303:HIV Reverse Transcriptase / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry*
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; C098320:efavirenz