原子与分子物理学报2017，Vol.34Issue(1)：130-135,6.DOI:103969/j.issn.1000-0364.2017.02.020
I50V变异对HIV-1蛋白酶抑制剂Amprenavir抗药机制的分子动力学研究
Probing drug resistance mechanism of I50V in HIV-1 protease on inhibitor Amprenavir by using molecular dynamics simulation
摘要
Abstract
Mutations in HIV-1 protease(PR) have produced drug resistance on current inhibitors and weaken inhibiting efficiency of anti-HIV drugs.In all mutations,I50V mutation is the most important one.This work adopts molecular dynamics (MD) simulations and solvated interaction energy(SIE) method to study the drug resistance of I50V mutation on Amprenavir.Dynamics analysis shows that I50V mutation strengthens overall flexibility and affects interaction of Amprenavir with residues in HIV-1 protease.Calculation of binding free energy indicates that the decrease in van der Waals interaction of Amprenavir with HIV-1 protease drives drug resistance of Amprenavir on the protease.The results form residue-based energy decomposition suggest that the interaction of V50/V50 in mutated PR with Amprenavir is obviously reduced relative to the wild-type PR,which implies that I50V mutation induces drug resistance.We expect that this study can provide theoretical guidance designs of potent inhibitors targeting HIV-1 protease.关键词
HIV-1蛋白酶/溶解相互作用能方法/分子动力学模拟/抗药性Key words
HIV-1 protease/Solvated interaction energy/Molecular dynamics simulation/Drug resistance分类
生物科学引用本文复制引用
吴世亮,梁志强,王伟,伊长虹,李洪云,赵娟..I50V变异对HIV-1蛋白酶抑制剂Amprenavir抗药机制的分子动力学研究[J].原子与分子物理学报,2017,34(1):130-135,6.基金项目
国家自然科学基金(11504206,11274206) （11504206,11274206）
山东省高等学校科技计划项目(J14LJ07) （J14LJ07）
