Higo J, Umeyama H
Department of Physical Chemistry, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Protein Eng. 1997 Apr;10(4):373-80. doi: 10.1093/protein/10.4.373.
To study the factors determining the collective motions in thermal, conformational fluctuations of a globular protein, molecular dynamics simulations were performed with a backbone model and an atomic-level model. In the backbone model, only the C alpha atoms were explicitly treated with two types of pairwise interactions assigned between the C alpha atoms; atom-packing interactions to take into account the effect of tight atom packing in the protein interior and chain-restoring interactions to maintain the backbone around the native conformation. A quasi-harmonic method was used to decompose the overall fluctuations into independent, collective modes. The modes assigned to large conformational fluctuations showed a good correlation between the backbone and atomic-level models. From this study, it was suggested that the collective modes were motions in which a protein fluctuates, keeping the tertiary structure around the native one and avoiding backbone overlap and, hence, rough aspects of the collective modes can be derived without details of the atomic interactions. The backbone model is useful in obtaining the overall backbone motions of a protein without heavy simulations, even though the simulation starts from a poorly determined conformation of experiments and in sampling main chain conformations, from which the side chain conformations may be predicted.
为了研究决定球状蛋白质热构象波动中集体运动的因素，我们使用主链模型和原子水平模型进行了分子动力学模拟。在主链模型中，仅对Cα原子进行显式处理，并在Cα原子之间分配了两种类型的成对相互作用；原子堆积相互作用以考虑蛋白质内部紧密原子堆积的影响，以及链恢复相互作用以维持天然构象周围的主链。使用准谐波方法将整体波动分解为独立的集体模式。分配给大构象波动的模式在主链模型和原子水平模型之间显示出良好的相关性。从这项研究中可以看出，集体模式是蛋白质波动的运动，保持围绕天然结构的三级结构并避免主链重叠，因此，无需原子相互作用的细节即可得出集体模式的大致情况。主链模型对于在不进行大量模拟的情况下获得蛋白质的整体主链运动很有用，即使模拟从实验确定不佳的构象开始，并且在对主链构象进行采样时，可以从中预测侧链构象。
