Prévost Chantal, Sacquin-Mora Sophie
CNRS, Laboratoire de Biochimie Théorique, UPR9080, Université de Paris, Paris, France.
Institut de Biologie Physico-Chimique, Fondation Edmond de Rothschild, PSL Research University, Paris, France.
Proteins. 2021 Oct;89(10):1315-1323. doi: 10.1002/prot.26152. Epub 2021 May 31.
The modeling of protein assemblies at the atomic level remains a central issue in structural biology, as protein interactions play a key role in numerous cellular processes. This problem is traditionally addressed using docking tools, where the quality of the models is based on their similarity to a single reference experimental structure. However, using a static reference does not take into account the dynamic quality of the protein interface. Here, we used all-atom classical Molecular Dynamics simulations to investigate the stability of the reference interface for three complexes that previously served as targets in the CAPRI competition. For each one of these targets, we also ran MD simulations for ten models that are distributed over the High, Medium and Acceptable accuracy categories. To assess the quality of these models from a dynamic perspective, we set up new criteria which take into account the stability of the reference experimental protein interface. We show that, when the protein interfaces are allowed to evolve along time, the original ranking based on the static CAPRI criteria no longer holds as over 50% of the docking models undergo a category change (which can be either toward a better or a lower accuracy group) when reassessing their quality using dynamic information.
在原子水平上对蛋白质组装体进行建模仍然是结构生物学中的核心问题，因为蛋白质相互作用在众多细胞过程中起着关键作用。传统上，这个问题是使用对接工具来解决的，模型的质量基于它们与单个参考实验结构的相似性。然而，使用静态参考并没有考虑到蛋白质界面的动态质量。在这里，我们使用全原子经典分子动力学模拟来研究三种复合物参考界面的稳定性，这三种复合物先前曾是CAPRI竞赛中的目标。对于这些目标中的每一个，我们还对分布在高、中、可接受精度类别的十个模型进行了分子动力学模拟。为了从动态角度评估这些模型的质量，我们建立了新的标准，该标准考虑了参考实验蛋白质界面的稳定性。我们表明，当允许蛋白质界面随时间演化时，基于静态CAPRI标准的原始排名不再成立，因为当使用动态信息重新评估对接模型的质量时，超过50%的对接模型会发生类别变化（可能朝着更高或更低精度组变化）。
