Grünberg Raik, Nilges Michael, Leckner Johan
Unité de Bioinformatique Structurale, CNRS URA 2185, Institut Pasteur, 25-28 rue du docteur Roux, F-75015 Paris, France.
Structure. 2006 Apr;14(4):683-93. doi: 10.1016/j.str.2006.01.014.
To better understand the interplay between protein-protein binding and protein dynamics, we analyzed molecular dynamics simulations of 17 protein-protein complexes and their unbound components. Complex formation does not restrict the conformational freedom of the partner proteins as a whole, but, rather, it leads to a redistribution of dynamics. We calculate the change in conformational entropy for seven complexes with quasiharmonic analysis. We see significant loss, but also increased or unchanged conformational entropy. Where comparison is possible, the results are consistent with experimental data. However, stringent error estimates based on multiple independent simulations reveal large uncertainties that are usually overlooked. We observe substantial gains of pseudo entropy in individual partner proteins, and we observe that all complexes retain residual stabilizing intermolecular motions. Consequently, protein flexibility has an important influence on the thermodynamics of binding and may disfavor as well as favor association. These results support a recently proposed unified model for flexible protein-protein association.
为了更好地理解蛋白质-蛋白质结合与蛋白质动力学之间的相互作用，我们分析了17种蛋白质-蛋白质复合物及其未结合组分的分子动力学模拟。复合物的形成并未整体限制伙伴蛋白的构象自由度，相反，它导致了动力学的重新分布。我们用准谐波分析计算了7种复合物的构象熵变化。我们看到了显著的损失，但也有构象熵增加或不变的情况。在可以进行比较的地方，结果与实验数据一致。然而，基于多个独立模拟的严格误差估计揭示了通常被忽视的巨大不确定性。我们观察到单个伙伴蛋白中有大量的伪熵增加，并且我们观察到所有复合物都保留了残余的稳定分子间运动。因此，蛋白质的灵活性对结合的热力学有重要影响，可能不利于也可能有利于缔合。这些结果支持了最近提出的关于柔性蛋白质-蛋白质缔合的统一模型。
