Molecular dynamics simulation and free energy calculations of symmetric fluoro-substituted diol-based HIV-1 protease inhibitors

被引:5
|
作者
Chen, Jian-Zhong [1 ]
Yang, Mao-You [1 ]
Yi, Chang-Hong [1 ]
Shi, Shu-Hua [1 ]
Zhang, Qing-Gang [1 ]
机构
[1] Shandong Normal Univ, Coll Phys & Elect, Jinan 250014, Peoples R China
来源
JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM | 2009年 / 899卷 / 1-3期
关键词
Molecular dynamics simulation; Binding free energy; HIV-1; protease; MM-PB/SA method; Fluoro-substitution; BINDING FREE-ENERGIES; CONTINUUM SOLVENT; POTENT INHIBITOR; AB-INITIO; MM-PBSA; RNA; STABILITY; LIGANDS; SURFACE;
D O I
10.1016/j.theochem.2008.11.029
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
HIV-1 protease has been an important drug target for the antiretroviral treatment of HIV infection over the years. Molecular dynamics simulations have been carried out to investigate the binding of six inhibitors to HIV-1 protease. The binding free energy of each complex was computed using the Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PB/SA) method. Our computations suggest that the fluoro-substitutions result in an increase in van der Waals interaction that dominates the binding free energy of each complex. Comparisons of the inhibitor-residue interactions of the fluoro-substituted inhibitors with the inhibitor BEB reveal that 3-, 2,4- and 2,5-fluoro-substitutions are helpful to combat the drug-resistant mutations on Ile50. The hydrogen bond analyses based on the trajectories of the dynamic simulations show the fluoro-substituted inhibitors can maintain the binding well. These data may assist in designing potent drugs to combat the drug-resistant mutations. (C) 2009 Elsevier B.V. All rights reserved.
引用
收藏
页码:1 / 8
页数:8
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