Chapter 4: Protein Interactions and Disease

Proteins do not function in isolation; it is their interactions with one another and also with other molecules (e.g. DNA, RNA) that mediate metabolic and signaling pathways, cellular processes, and organismal systems. Due to their central role in biological function, protein interactions also control the mechanisms leading to healthy and diseased states in organisms. Diseases are often caused by mutations affecting the binding interface or leading to biochemically dysfunctional allosteric changes in proteins. Therefore, protein interaction networks can elucidate the molecular basis of disease, which in turn can inform methods for prevention, diagnosis, and treatment. In this chapter, we will describe the computational approaches to predict and map networks of protein interactions and briefly review the experimental methods to detect protein interactions. We will describe the application of protein interaction networks as a translational approach to the study of human disease and evaluate the challenges faced by these approaches.蛋白质并非孤立行使功能：正是它们彼此之间，以及与其他分子（如脱氧核糖核酸(DNA)、核糖核酸(RNA)）之间的相互作用，介导了代谢与信号通路、细胞过程以及生物体系统的正常运作。鉴于蛋白质在生物功能中扮演核心角色，蛋白质相互作用同样调控着生物体健康与疾病状态背后的分子机制。疾病往往由突变引发，这些突变要么影响蛋白质的结合界面，要么导致蛋白质发生生化功能异常的别构改变。因此，蛋白质相互作用网络能够阐明疾病的分子基础，进而为疾病的预防、诊断与治疗方法提供理论依据。在本章节中，我们将介绍用于预测和绘制蛋白质相互作用网络的计算方法，并简要综述检测蛋白质相互作用的实验手段。我们还将阐述蛋白质相互作用网络作为转化研究手段在人类疾病研究中的应用，并评估这些方法所面临的挑战。