Microsecond molecular dynamics simulation shows effect of slow loop dynamics on backbone amide order parameters of proteins
Microsecond molecular dynamics simulation shows effect of slow loop dynamics on backbone amide order parameters of proteins
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DOI：
10.1021/jp077018h
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发表时间：
2008-05-15
影响因子：
3.3
通讯作者：
Shaw, David E.
中科院分区：
文献类型：
--
作者：
Maragakis, Paul;Lindorff-Larsen, Kresten;Shaw, David E.
从分子水平上理解蛋白质的功能需要了解其结构和动力学性质。核磁共振光谱学允许测量广义有序参数，这些参数提供了对蛋白质结构中皮秒和纳秒波动的原子描述。分子动力学(MD)模拟为在相似的时间尺度上研究蛋白质动力学提供了一种补充方法。核磁共振波谱和MD模拟之间的比较可以用来解释实验结果，并改进与模拟相关的力场和积分方法的质量。然而，从模拟和实验中提取的序参数之间的明显系统差异是常见的，特别是对于非正则二级结构的元素。在本文中，对蛋白质泛素的1.2MU S显式溶剂MD模拟的结果与先前由核磁共振弛豫实验得到的骨架有序参数进行了比较[Tjandra，N.；Feller，S.E.；Pastor，R.W.；BAX，A.J.Am化学。SoC。1995年、117年、12562-12566年]。模拟揭示了三个环区的涨落，这些涨落发生在与泛素整体旋转扩散相当或更长的时间尺度上，其影响在实验得出的序参数中不明显。内部运动和整体运动的耦合分析产生的模拟序参数比传统的单独分析内部运动的情况更接近于实验确定的值。从评估长MD模拟的准确性的角度来看，模拟和实验之间的一致性的改善也是令人鼓舞的。
A molecular-level understanding of the function of a protein requires knowledge of both its structural and dynamic properties. NMR spectroscopy allows the measurement of generalized order parameters that provide an atomistic description of picosecond and nanosecond fluctuations in protein structure. Molecular dynamics (MD) simulation provides a complementary approach to the study of protein dynamics on similar,time scales. Comparisons between NMR spectroscopy and MD simulations can be used to interpret experimental results and to improve the quality of simulation-related force fields and integration methods. However, apparent systematic discrepancies between order parameters extracted from simulations and experiments are common, particularly for elements of noncanonical secondary structure. In this paper, results from a 1.2 mu s explicit solvent MD simulation of the protein ubiquitin are compared with previously determined backbone order parameters derived from NMR relaxation experiments [Tjandra, N.; Feller, S. E.; Pastor, R. W.; Bax, A. J. Am. Chem. Soc. 1995, 117, 12562-12566]. The simulation reveals fluctuations in three loop regions that occur on time scales comparable to or longer than that of the overall rotational diffusion of ubiquitin and whose effects would not be apparent in experimentally derived order parameters. A coupled analysis of internal and overall motion yields simulated order parameters substantially closer to the experimentally determined values than is the case for a conventional analysis of internal motion alone. Improved agreement between simulation and experiment also is encouraging from the viewpoint of assessing the accuracy of long MD simulations.