马拉维洛克
CCR5受体拮抗剂
分子动力学
化学
对接(动物)
合理设计
立体化学
人类免疫缺陷病毒(HIV)
受体
趋化因子受体
计算化学
病毒学
生物
生物化学
纳米技术
医学
材料科学
趋化因子
护理部
作者
Qifeng Bai,Yang Zhang,Yongming Li,Wenbo Chen,Huanxiang Liu,Xiaojun Yao
摘要
C–C chemokine receptor type 5 (CCR5) is the co-receptor of human immunodeficiency virus type 1 (HIV-1) and plays an important role in HIV-1 virus infection. Maraviroc has been proved to be effective for anti-HIV-1 by targeting CCR5. Understanding the detailed interaction mechanism between CCR5 and Maraviroc will be of great help to the rational design of a more potential inverse agonist to block HIV-1 infection. Here, we performed molecular dynamics (MD) simulation and accelerated MD simulation (aMD) to study the interaction mechanism between CCR5 and Maraviroc based on a recently reported crystal structure. The results of MD simulation demonstrate that Maraviroc can form stable hydrogen bonds with residues Tyr371.39, Tyr2516.51 and Glu2837.39. The results of aMD simulation indicate that the carboxamide moiety is more flexible than the tropane group of Maraviroc in the pocket of CCR5. The electrostatic potential analysis proves that Maraviroc can escape from the pocket of CCR5 along the negative electrostatic potential pathway during the dissociation process. The free energy calculation illustrates that there exist three binding pockets during the dissociation process of Maraviroc. Our results will be useful for understanding the interaction mechanism between CCR5 and Maraviroc as well as for the rational design of a more potent inverse agonist.
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