Ozdemir E Sila, Halakou Farideh, Nussinov Ruth, Gursoy Attila, Keskin Ozlem
Department of Chemical and Biological Engineering, Koc University, Istanbul, Turkey.
Department of Computer Engineering, Koc University, Istanbul, Turkey.
Methods Mol Biol. 2019;1903:1-21. doi: 10.1007/978-1-4939-8955-3_1.
Drug repurposing is a creative and resourceful approach to increase the number of therapies by exploiting available and approved drugs. However, identifying new protein targets for previously approved drugs is challenging. Although new strategies have been developed for drug repurposing, there is broad agreement that there is room for further improvements. In this chapter, we review protein-protein interaction (PPI) interface-targeting strategies for drug repurposing applications. We discuss certain features, such as hot spot residue and hot region prediction and their importance in drug repurposing, and illustrate common methods used in PPI networks to identify drug off-targets. We also collect available online resources for hot spot prediction, binding pocket identification, and interface clustering which are effective resources in polypharmacology. Finally, we provide case studies showing the significance of protein interfaces and hot spots in drug repurposing.
药物再利用是一种通过利用现有且已获批的药物来增加治疗方法数量的创新且机智的方法。然而，为先前已获批的药物确定新的蛋白质靶点具有挑战性。尽管已经开发出了用于药物再利用的新策略，但人们普遍认为仍有进一步改进的空间。在本章中，我们回顾了用于药物再利用应用的蛋白质-蛋白质相互作用（PPI）界面靶向策略。我们讨论了某些特征，例如热点残基和热点区域预测及其在药物再利用中的重要性，并说明了在PPI网络中用于识别药物脱靶的常用方法。我们还收集了用于热点预测、结合口袋识别和界面聚类的可用在线资源，这些资源在多药理学中是有效的资源。最后，我们提供了案例研究，展示了蛋白质界面和热点在药物再利用中的重要性。
