In the crowded cell, a strong selective pressure operates on the proteome to limit the competition between functional and non-functional protein-protein interactions. We developed an original theoretical framework in order to interrogate how this competition constrains the behavior of proteins with respect to their partners or random encounters. Our theoretical framework relies on a two-dimensional (2D) representation of interaction energy landscapes, with 2D energy maps, which reflect in a synthetic way the spatial distribution of the interaction propensity of a protein surface for another protein. We realized the interaction propensity mapping of proteins' surfaces in interaction with functional and arbitrary partners and asked whether the distribution of their interaction propensity is conserved during evolution. Therefore, we performed several thousands of cross-docking simulations to systematically characterize the energy landscapes of 103 proteins interacting with different sets of homologs, corresponding to their functional partner's family or arbitrary protein families. Then, we systematically compared the energy maps resulting from the docking of each protein with the different protein families of the dataset. Strikingly, we show that the interaction propensity not only of the binding sites but also of the rest of the surface is conserved for docking partners belonging to the same protein family. Interestingly, this observation holds for docked proteins corresponding to true but also arbitrary partners. Our theoretical framework enables the characterization of the energy behavior of a protein in interaction with hundreds of proteins and opens the way for the characterization of the behavior of proteins in a specific environment.

中文翻译：

---

蛋白质相互作用的能量格局由功能性和非功能性伙伴塑造。

在拥挤的细胞中，强大的选择性压力作用于蛋白质组，以限制功能性和非功能性蛋白质-蛋白质相互作用之间的竞争。我们开发了一个原始的理论框架，以询问这种竞争如何限制蛋白质相对于其伴侣或随机遭遇的行为。我们的理论框架依赖于交互能量图的二维（2D）表示，带有二维能量图，该图以合成方式反映了蛋白质表面与另一种蛋白质的相互作用倾向的空间分布。我们实现了蛋白质表面与功能伙伴和任意伙伴相互作用的相互作用倾向图，并询问在进化过程中它们相互作用倾向的分布是否保守。因此，我们进行了数千次跨码头模拟，以系统地表征103种蛋白质的能量构象，这些蛋白质与不同的同系物（与其功能伙伴的家族或任意蛋白家族）相对应。然后，我们系统地比较了每种蛋白质与数据集的不同蛋白质家族对接产生的能量图。令人惊讶地，我们表明，对于相同蛋白质家族的对接伴侣，不仅结合位点的相互作用倾向而且表面的其余部分的相互作用倾向都得以保留。有趣的是，该观察结果适用于与真实但任意伴侣相对应的对接蛋白质。