抑制剂Amprenavir与HIV-2蛋白酶作用机制的分子动力学研究

Molecular Dynamics Insight into The Interaction Mechanism of Inhibitor Amprenavir with HIV-2 Protease

HIV-2蛋白酶已成为治疗艾滋病的一个重要药物靶标。作者采用分子动力学模拟并结合自由能计算,研究了抑制剂Amprenavir(AMP)与HIV-2蛋白酶的作用机制。研究结果表明范德华作用是AMP与HIV-2蛋白酶结合的主要力量。采用基于残基的自由能分解方法计算抑制剂-残基相互作用,结果表明疏水性的CH-π和CH-O相互作用驱动了抑制剂AMP与HIV-2蛋白酶的结合。作者期望这一研究结果能为抗艾滋病双重抑制剂的研发提供一定的理论指导。

HIV-2 protease （PR2） has been an important target for the design of drugs curing AIDS. Molecular dynamics simulations combined with calculation of binding free energy were carried out to study the interaction mechanism of inhibitor AMP with PR2, the results suggested that van der Waals interaction is the main force of the binding of AMP to PR2. Residue-based free energy decomposition method was also applied to calculate the inhibitor-residue interaction, and the results showed that the interaction of hydrophobic CH-π and CH-O drives the binding of AMP to PR2. The authors expect that this study can provide theoretical hint for the design of dual inhibitors of anti-AIDS.