title: Comparative study of some energetic and steric parameters of the wild type and mutants HIV-1 protease: a way to explain the viral resistance.
abstract: Because, in vivo, the HIV-1 PR ( HIV-1 protease) present a high mutation rate we performed a comparative study of the energetic behaviors of the wild type HIV-1 PR and four type of mutants: Val82/Asn; Val82/Asp; Gln7/Lys, Leu33/Ile, Leu63/Ile; Ala71/Thr, Val82/Ala. We suggest that the energetic fluctuation (electrostatic, van der Waals and torsion energy) of the mutants and the solvent accessible surface (SAS) values can be useful to explain the viral resistance process developed by HIV-1 PR. The number and localization of enzyme mutations induce important modifications of the van der Waals and torsional energy, while the electrostatic energy has an insignificant fluctuation. We showed that the viral resistance can be explored if the solvent accessible surfaces of the active site for the mutant structures are calculated. In this paper we have obtained the solvent accessible surface for a group of 15 mutants (11 mutants obtained by Protein Data Bank (PDB) file, 4 mutants modeled by CHARMM software) and for the wild type HIV-1 PR). Our study try to show that the number and localization of the mutations are factors which induce the HIV-1 PR viral resistance. The larger solvent accessible surface could be recorded for the point mutant Val 82/Phe.
authors.affiliation: Department of Physiology and Biophysics, University of Bucharest, Faculty of Biology, Splaiul Independentei 91-95, Bucharest, R-76201, Romania. speranta@bio.bio.unibuc.ro
authors.forename: Speranta
authors.initials: S
authors.lastname: Avram
authors.forename: L
authors.initials: L
authors.lastname: Movileanu
authors.forename: D
authors.initials: D
authors.lastname: Mihailescu
authors.forename: Maria-Luiza
authors.initials: ML
authors.lastname: Flonta
mesh_terms: D019943:Amino Acid Substitution; D001665:Binding Sites; D004352:Drug Resistance, Microbial; D016333:HIV Protease / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000201:enzymology*; D006801:Humans; D008958:Models, Molecular; D017354:Point Mutation; D017433:Protein Structure, Secondary; D055672:Static Electricity; D013329:Structure-Activity Relationship
chemical_list: D016333:HIV Protease