What contributions to protein side-chain dynamics are probed by NMR experiments? A molecular dynamics simulation analysis
What contributions to protein side-chain dynamics are probed by NMR experiments? A molecular dynamics simulation analysis
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DOI：
10.1016/j.jmb.2005.03.001
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发表时间：
2005-05-27
影响因子：
5.6
通讯作者：
Karplus, M
中科院分区：
文献类型：
--
作者：
Best, RB;Clarke, J;Karplus, M
结构同源蛋白TNfn3和FNfn10的分子动力学模拟已被用来研究侧链动力学的NMR弛豫实验测量的贡献。结果再现了核侧链动态观察到的NMR的变化，并突出了非谐运动和解释NMR侧链序参数的局部极小值之间的过渡的相关性。本文介绍了一种利用复制交换分子动力学结合隐式溶剂模型计算收敛序参数的方法。这些模拟允许通过扰动系统来测试各种因素（例如侧链的柔性及其自由体积）对迁移率的影响。发现缺失突变对更密集的FNfn10具有最大的影响。一些违反直觉的影响，如增加的顺序参数接近缺失突变位点，但这些可以合理化的直接相互作用与修改的侧链。公布的顺序参数的统计分析支持从模拟得出的结论。(c)2005爱思唯尔有限公司保留所有权利。
Molecular dynamics simulations of the structurally homologous proteins TNfn3 and FNfn10 have been used to investigate the contributions to side-chain dynamics measured by NMR relaxation experiments. The results reproduce the variation in core side-chain dynamics observed by NMR and highlight the relevance of anharmonic motion and transitions between local minima for explaining NMR side-chain order parameters. A method is described for calculating converged order parameters by use of replica exchange molecular dynamics in conjunction with an implicit solvent model. These simulations allow the influence of various factors, such as the flexibility of side-chains and their free volume, on the mobility to be tested by perturbing the system. Deletion mutations are found to have the largest effect on the more densely packed FNfn10. Some counterintuitive effects are seen, such as an increase in order parameters close to deletion mutation sites, but these can be rationalized in terms of direct interactions with the modified side-chains. A statistical analysis of published order parameters supports the conclusions drawn from the simulations. (c) 2005 Elsevier Ltd. All rights reserved.