Efficient characterization of collective motions and interresidue correlations in proteins by low-resolution simulations
Efficient characterization of collective motions and interresidue correlations in proteins by low-resolution simulations
复制标题
DOI：
10.1021/bi971611f
复制
发表时间：
1997-11-04
期刊：
影响因子：
2.9
通讯作者：
Jernigan, RL
中科院分区：
文献类型：
--
作者：
Bahar, I;Erman, B;Jernigan, RL
低分辨率模型与最近开发的基于知识的潜力一起用于探索蛋白质的动力学。配置是使用蒙特卡罗/Metropolis 方案与奇异值分解技术 (SVD) 相结合生成的。该方法可以详细描述协作运动的特征，比原子模拟至少快 1 个数量级。轨迹被划分为模式，并分析最慢的模式，以阐明集体运动的主导机制。对噬菌体 T4 溶菌酶（一种双结构域酶）进行的计算表明，每个结构域内的结构元件都受到强耦合运动的影响，而两个结构域相对于彼此的运动是强烈反相关的。这种类型的运动，由域质心在相反方向上同步波动高达 +/-4.0 埃所证明，与最近在溶液中的自旋标记实验观察到的运动相当。控制这些波动的平均力的潜力被证明是非调和的。 N端结构域的β-折叠区域和C端结构域的螺旋E被认为是对于介导协作运动很重要的区域，特别是对于结构域之间活性位点裂缝的打开和关闭。中央螺旋 C 中的残基 Leu66-Phe67 阻止域之间相关运动的传播。模拟揭示的参与高度协作运动的基团与通过脉冲 H/D 交换和 2-D NMR 测量的展开过程中高度受保护的区域之间存在相关性。
A low-resolution model is used together with recently developed knowledge-based potentials for exploring the dynamics of proteins. Configurations are generated using a Monte Carlo/Metropolis scheme combined with a singular value decomposition technique (SVD). The approach is shown to characterize the cooperative motions in good detail, at least 1 order of magnitude faster than atomic simulations. Trajectories are partitioned into modes, and the slowest ones are analyzed to elucidate the dominant mechanism of collective motions. Calculations performed for bacteriophage T4 lysozyme, a two-domain enzyme, demonstrate that the structural elements within each domain are subject to strongly coupled motions, whereas the motions of the two domains with respect to each other are strongly anticorrelated. This type of motion, evidenced by the synchronous fluctuations of the domain centroids by up to +/-4.0 Angstrom in opposite directions, is comparable to the movements observed by recent spin-labeling experiments in solution. The potential of mean force governing these fluctuations is shown to be anharmonic. The beta-sheet region at the N-terminal domain and the helix E in the C-terminal domain are identified as regions important for mediating cooperative motions and, in particular, for the opening and closing of the active-site cleft between the domains. Residues Leu66-Phe67 in the central helix C stop the propagation of correlated motions between the domains. There is a correlation between the groups involved in highly cooperative motions revealed by simulations and the highly protected regions during unfolding measured by pulsed H/D exchange and 2-D NMR.