Comparative study of some energetic and steric parameters of the wild type and mutants HIV-1 protease: a way to explain the viral resistance

被引:8
作者
Avram, S
Movileanu, L
Mihailescu, D
Flonta, ML
机构
[1] Univ Bucharest, Dept Physiol & Biophys, Fac Biol, R-76201 Bucharest, Romania
[2] Texas A&M Univ, Hlth Sci Ctr, College Stn, TX USA
关键词
genomics; genetic code; genomic signals; complex representation; phase analysis; unwrapped phase; sequence path;
D O I
10.1111/j.1582-4934.2002.tb00192.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Because, in vivo, the HIV-2 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, Va182/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 (I I 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.
引用
收藏
页码:251 / 260
页数:10
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