Computational Biology and Clinical Informatics, Baker Heart and Diabetes Institute, Melbourne, Victoria.
Systems and Computational Biology, Bio21 Institute, University of Melbourne, Melbourne, Victoria.
Brief Bioinform. 2022 Jul 18;23(4). doi: 10.1093/bib/bbac165.
Proteins are capable of highly specific interactions and are responsible for a wide range of functions, making them attractive in the pursuit of new therapeutic options. Previous studies focusing on overall geometry of protein-protein interfaces, however, concluded that PPI interfaces were generally flat. More recently, this idea has been challenged by their structural and thermodynamic characterisation, suggesting the existence of concave binding sites that are closer in character to traditional small-molecule binding sites, rather than exhibiting complete flatness. Here, we present a large-scale analysis of binding geometry and physicochemical properties of all protein-protein interfaces available in the Protein Data Bank. In this review, we provide a comprehensive overview of the protein-protein interface landscape, including evidence that even for overall larger, more flat interfaces that utilize discontinuous interacting regions, small and potentially druggable pockets are utilized at binding sites.
蛋白质具有高度特异性的相互作用，并负责广泛的功能，这使得它们成为新的治疗选择的有吸引力的目标。然而，以前的研究集中在蛋白质-蛋白质界面的整体几何形状上，得出的结论是 PPI 界面通常是平坦的。最近，这一观点受到了它们的结构和热力学特征的挑战，这表明存在凹形结合位点，这些结合位点更接近传统的小分子结合位点，而不是表现出完全的平坦性。在这里，我们对蛋白质数据库中所有蛋白质-蛋白质界面的结合几何形状和物理化学性质进行了大规模分析。在这篇综述中，我们提供了蛋白质-蛋白质界面景观的全面概述，包括证据表明，即使对于整体上更大、更平坦的界面，利用不连续的相互作用区域，在结合位点也会利用小的、潜在可成药的口袋。
