title: Binding energy analysis for wild-type and Y181C mutant HIV-1 RT/8-Cl TIBO complex structures: quantum chemical calculations based on the ONIOM method.
abstract: Two-layered and three-layered ONIOM calculations were performed to compare the binding energies of 8-Cl TIBO inhibitor when bound into the human immunodeficiency virus reverse transcriptase binding pocket and a Y181C variant. Both consisted of 20 residues within a radius of 15 A. A combination of different methods [MP2/6-31G(d), B3LYP/6-31G(d,p), and PM3] were performed to take advantage of ONIOM's layering strategy analysis. The obtained results clearly indicate that the Y181C mutation reduces the binding affinity and stability of the inhibitor by approximately 8-9 kcal/mol as obtained from different combined MO:MO methods. Analyses regarding the energetic components of the interaction and deformation energies for 8-Cl TIBO inhibitor upon binding were also examined extensively. Additional calculations involving the interaction energies between 8-Cl TIBO with individual residues surrounding the binding pocket were performed at MP2/6-31G(d,p) and B3LYP/6-31G(d,p) levels of theory to gain more insight into the energetic differences of wild-type and Y181C mutant type at the atomistic level.
authors.affiliation: Chemistry Department, Faculty of Science, Kasetsart University, Bangkok, Thailand.
authors.forename: Suwipa
authors.initials: S
authors.lastname: Saen-oon
authors.forename: Mayuso
authors.initials: M
authors.lastname: Kuno
authors.forename: Supa
authors.initials: S
authors.lastname: Hannongbua
mesh_terms: D019943:Amino Acid Substitution; D019281:Dimerization; D015497:HIV-1 / Q000201:enzymology*; D007700:Kinetics; D008958:Models, Molecular; D020641:Polymorphism, Single Nucleotide; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D011789:Quantum Theory; D012194:RNA-Directed DNA Polymerase / Q000737:chemistry* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D013816:Thermodynamics
chemical_list: D021122:Protein Subunits; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; D012194:RNA-Directed DNA Polymerase