Coarse-Grained Molecular Dynamics Simulations of Protein-Ligand Binding
Coarse-Grained Molecular Dynamics Simulations of Protein-Ligand Binding
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DOI：
10.1002/jcc.23693
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发表时间：
2014-09-30
影响因子：
3
通讯作者：
Terada, Tohru
中科院分区：
文献类型：
--
作者：
Negami, Tatsuki;Shimizu, Kentaro;Terada, Tohru
采用MARTINI力场进行了粗粒度分子动力学（CGMD）模拟，再现了蛋白质与配体的结合过程。我们选择了两种蛋白质-配体系统，左旋蔗糖-糖（葡萄糖或蔗糖）和linb -1,2-二氯乙烷系统，作为靶系统，它们在配体结合袋的大小和形状以及袋和配体的物理化学性质方面有所不同。粗粒（CG）配体分子的空间分布揭示了蛋白质表面潜在的配体结合位点，而不是真正的配体结合位点。配体与真正的配体结合位点结合最强烈。左旋蔗糖-蔗糖体系的CGMD模拟得到的结合和解结合速率常数约为实验值的10倍；这主要是由于CG配体在CG水模型中的扩散速度更快。我们可以得到两种体系的解离常数接近实验值。配体通量分析表明，CG配体分子通过特定途径进入配体结合袋。配体倾向于通过蛋白质表面的凹槽移动。因此，总的来说，CGMD模拟对两种不同的系统产生了合理的结果，对研究蛋白质-配体结合过程是有用的。(C) 2014 Wiley期刊公司
Coarse-grained molecular dynamics (CGMD) simulations with the MARTINI force field were performed to reproduce the protein-ligand binding processes. We chose two protein-ligand systems, the levansucrase-sugar (glucose or sucrose), and LinB-1,2-dichloroethane systems, as target systems that differ in terms of the size and shape of the ligand-binding pocket and the physicochemical properties of the pocket and the ligand. Spatial distributions of the Coarse-grained (CG) ligand molecules revealed potential ligand-binding sites on the protein surfaces other than the real ligand-binding sites. The ligands bound most strongly to the real ligand-binding sites. The binding and unbinding rate constants obtained from the CGMD simulation of the levansucrase-sucrose system were approximately 10 times greater than the experimental values; this is mainly due to faster diffusion of the CG ligand in the CG water model. We could obtain dissociation constants close to the experimental values for both systems. Analysis of the ligand fluxes demonstrated that the CG ligand molecules entered the ligand-binding pockets through specific pathways. The ligands tended to move through grooves on the protein surface. Thus, the CGMD simulations produced reasonable results for the two different systems overall and are useful for studying the protein-ligand binding processes. (C) 2014 Wiley Periodicals, Inc.