UMR7374 Interfaces, Confinement, Matériaux et Nanostructures, Université d'Orléans, Orléans, France.
UMR6004 Laboratoire des Sciences du Numérique de Nantes, Nantes, France.
Sci Rep. 2022 Nov 9;12(1):19057. doi: 10.1038/s41598-022-21648-9.
Intrinsically disordered proteins (IDP) are at the center of numerous biological processes, and attract consequently extreme interest in structural biology. Numerous approaches have been developed for generating sets of IDP conformations verifying a given set of experimental measurements. We propose here to perform a systematic enumeration of protein conformations, carried out using the TAiBP approach based on distance geometry. This enumeration was performed on two proteins, Sic1 and pSic1, corresponding to unphosphorylated and phosphorylated states of an IDP. The relative populations of the obtained conformations were then obtained by fitting SAXS curves as well as Ramachandran probability maps, the original finite mixture approach RamaMix being developed for this second task. The similarity between profiles of local gyration radii provides to a certain extent a converged view of the Sic1 and pSic1 conformational space. Profiles and populations are thus proposed for describing IDP conformations. Different variations of the resulting gyration radius between phosphorylated and unphosphorylated states are observed, depending on the set of enumerated conformations as well as on the methods used for obtaining the populations.
无规则蛋白质（IDP）是许多生物过程的核心，因此在结构生物学中引起了极大的关注。已经开发了许多方法来生成一组验证给定实验测量的 IDP 构象。在这里，我们提议使用基于距离几何的 TAiBP 方法进行蛋白质构象的系统枚举。这项枚举是针对两种蛋白质 Sic1 和 pSic1 进行的，它们分别对应于 IDP 的未磷酸化和磷酸化状态。然后通过拟合 SAXS 曲线以及 Ramachandran 概率图来获得获得构象的相对丰度，原始的有限混合方法 RamaMix 就是为此第二个任务而开发的。局部回转半径曲线的相似性在一定程度上提供了 Sic1 和 pSic1 构象空间的收敛视图。因此，提出了用于描述 IDP 构象的分布和丰度。在磷酸化和非磷酸化状态之间，观察到不同的回转半径变化，这取决于枚举的构象集以及用于获得丰度的方法。
