Open AccessComparative study of some energetic and steric parameters of the wild type and mutants HIV‐1 protease: a way to explain the viral resistance
Author(s) -
Avram Speranta,
Movileanu L.,
Mihailescu D.,
Flonta MariaLuiza
Publication year - 2002
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2002.tb00192.x
Subject(s) - mutant , protein data bank (rcsb pdb) , wild type , hiv 1 protease , chemistry , van der waals force , solvent , accessible surface area , steric effects , protease , biophysics , virology , biology , stereochemistry , computational chemistry , enzyme , biochemistry , molecule , organic chemistry , gene
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.