Graduate School of Informatics, Department of Health Informatics, METU, Ankara, Turkey; Cancer Systems Biology Laboratory (CanSyL-METU), Ankara, Turkey.
Curr Top Med Chem. 2018;18(8):700-713. doi: 10.2174/1568026618666180601080824.
Protein-Protein Interactions (PPIs) are the key components in many cellular processes including signaling pathways, enzymatic reactions and epigenetic regulation. Abnormal interactions of some proteins may be pathogenic and cause various disorders including cancer and neurodegenerative diseases. Although inhibiting PPIs with small molecules is a challenging task, it gained an increasing interest because of its strong potential for drug discovery and design. The knowledge of the interface as well as the structural and chemical characteristics of the PPIs and their roles in the cellular pathways is necessary for a rational design of small molecules to modulate PPIs. In this study, we review the recent progress in the field and detail the physicochemical properties of PPIs including binding hot spots with a focus on structural methods. Then, we review recent approaches for structural prediction of PPIs. Finally, we revisit the concept of targeting PPIs from a systems biology perspective and we refer to approaches that are usually employed when the structural information is not present.
蛋白质-蛋白质相互作用（PPIs）是许多细胞过程的关键组成部分，包括信号通路、酶反应和表观遗传调控。一些蛋白质的异常相互作用可能是致病的，并导致各种疾病，包括癌症和神经退行性疾病。尽管用小分子抑制 PPIs 是一项具有挑战性的任务，但由于其在药物发现和设计方面的巨大潜力，它越来越受到关注。了解 PPI 的界面以及它们在细胞途径中的结构和化学特性，对于合理设计小分子来调节 PPI 是必要的。在这项研究中，我们回顾了该领域的最新进展，并详细介绍了 PPI 的物理化学性质，包括结合热点，并重点介绍了结构方法。然后，我们回顾了 PPI 结构预测的最新方法。最后，我们从系统生物学的角度重新审视了靶向 PPI 的概念，并提到了在没有结构信息时通常采用的方法。
