利用计算机模拟工作流程探索蛋白质-蛋白质相互作用作为抗癌治疗的药物靶点
Exploring Protein-Protein Interactions as Drug Targets for Anti-cancer Therapy with In Silico Workflows.
作者信息
Goncearenco Alexander, Li Minghui, Simonetti Franco L, Shoemaker Benjamin A, Panchenko Anna R
机构信息
National Center for Biotechnology Information, National Institutes of Health, Bethesda, MD, 20894, USA.
School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China.
出版信息
Methods Mol Biol. 2017;1647:221-236. doi: 10.1007/978-1-4939-7201-2_15.
Abstract
We describe a computational protocol to aid the design of small molecule and peptide drugs that target protein-protein interactions, particularly for anti-cancer therapy. To achieve this goal, we explore multiple strategies, including finding binding hot spots, incorporating chemical similarity and bioactivity data, and sampling similar binding sites from homologous protein complexes. We demonstrate how to combine existing interdisciplinary resources with examples of semi-automated workflows. Finally, we discuss several major problems, including the occurrence of drug-resistant mutations, drug promiscuity, and the design of dual-effect inhibitors.
摘要
我们描述了一种计算协议，以辅助设计针对蛋白质-蛋白质相互作用的小分子和肽类药物，特别是用于抗癌治疗。为实现这一目标，我们探索了多种策略，包括寻找结合热点、纳入化学相似性和生物活性数据，以及从同源蛋白质复合物中采样相似的结合位点。我们通过半自动工作流程的示例展示了如何整合现有的跨学科资源。最后，我们讨论了几个主要问题，包括耐药突变的发生、药物混杂性以及双效抑制剂的设计。
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