Liu Qing, Shi Chaowei, Yu Lu, Zhang Longhua, Xiong Ying, Tian Changlin
Hefei National Laboratory for Physical Sciences at The Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230026, PR China.
Hefei National Laboratory for Physical Sciences at The Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230026, PR China; High Magnetic Field Laboratory, Chinese Academy of Science, Hefei, Anhui, 230031, PR China.
Biochem Biophys Res Commun. 2015 Feb 13;457(3):467-72. doi: 10.1016/j.bbrc.2015.01.018. Epub 2015 Jan 17.
Internal backbone dynamic motions are essential for different protein functions and occur on a wide range of time scales, from femtoseconds to seconds. Molecular dynamic (MD) simulations and nuclear magnetic resonance (NMR) spin relaxation measurements are valuable tools to gain access to fast (nanosecond) internal motions. However, there exist few reports on correlation analysis between MD and NMR relaxation data. Here, backbone relaxation measurements of (15)N-labeled SH3 (Src homology 3) domain proteins in aqueous buffer were used to generate general order parameters (S(2)) using a model-free approach. Simultaneously, 80 ns MD simulations of SH3 domain proteins in a defined hydrated box at neutral pH were conducted and the general order parameters (S(2)) were derived from the MD trajectory. Correlation analysis using the Gromos force field indicated that S(2) values from NMR relaxation measurements and MD simulations were significantly different. MD simulations were performed on models with different charge states for three histidine residues, and with different water models, which were SPC (simple point charge) water model and SPC/E (extended simple point charge) water model. S(2) parameters from MD simulations with charges for all three histidines and with the SPC/E water model correlated well with S(2) calculated from the experimental NMR relaxation measurements, in a site-specific manner.
蛋白质内部主链的动态运动对于不同的蛋白质功能至关重要，且发生在从飞秒到秒的广泛时间尺度上。分子动力学（MD）模拟和核磁共振（NMR）自旋弛豫测量是获取快速（纳秒级）内部运动信息的重要工具。然而，关于MD和NMR弛豫数据之间相关性分析的报道较少。在此，利用无模型方法，对在水性缓冲液中（15）N标记的SH3（Src同源3）结构域蛋白进行主链弛豫测量，以生成广义序参数（S(2)）。同时，在中性pH下的特定水合盒中对SH3结构域蛋白进行了80纳秒的MD模拟，并从MD轨迹中导出广义序参数（S(2)）。使用Gromos力场进行的相关性分析表明，NMR弛豫测量和MD模拟得到的S(2)值存在显著差异。对三个组氨酸残基具有不同电荷状态的模型以及使用不同水模型（即SPC（简单点电荷）水模型和SPC/E（扩展简单点电荷）水模型）进行了MD模拟。在所有三个组氨酸均带电荷且使用SPC/E水模型的MD模拟中得到的S(2)参数，与通过实验NMR弛豫测量计算得到的S(2)以位点特异性方式具有良好的相关性。
