Abstract：
The interactions of G-protein-coupled receptors (GPCRs) with other proteins are critical in several cellular processes but resolving their structural dynamics remains challenging. An increasing number of GPCR complexes have been experimentally resolved but others including receptor variants are yet to be characterized, necessitating computational predictions of their interactions. Although integrative approaches with multi-scale simulations would provide rigorous estimates of their conformational dynamics, protein-protein docking remains a first tool of choice of many researchers due to the availability of open-source programs and easy to use web servers with reasonable predictive power. Protein-protein docking algorithms have limited ability to consider protein flexibility, environment effects, and entropy contributions and are usually a first step towards more integrative approaches. The two critical steps of docking: the sampling and scoring algorithms have improved considerably and their performance has been validated against experimental data. In this chapter, we provide an overview and generalized protocol of a few docking protocols using GPCRs as test cases. In particular, we demonstrate the interactions of GPCRs with extracellular protein ligands and an intracellular protein effectors (G-protein) predicted from docking approaches and test their limitations. The current chapter will help researchers critically assess docking protocols and predict experimentally testable structures of GPCR complexes.
摘要：
G蛋白偶联受体（GPCRs）与其他蛋白质的相互作用在几种细胞过程中至关重要，但解决其结构动力学仍然具有挑战性。越来越多的GPCR复合物已通过实验解析，但其他包括受体变体在内的尚未表征。需要对它们的相互作用进行计算预测。尽管具有多尺度模拟的综合方法将提供对其构象动力学的严格估计，蛋白质-蛋白质对接仍然是许多研究人员选择的首选工具，因为开源程序和易于使用的Web服务器具有合理的预测能力。蛋白质-蛋白质对接算法考虑蛋白质灵活性的能力有限，环境影响,和熵的贡献，通常是迈向更综合的方法的第一步。对接的两个关键步骤：采样和评分算法有了很大的改进，并且它们的性能已经通过实验数据得到了验证。在这一章中,我们提供了一些使用GPCRs作为测试用例的对接协议的概述和通用协议。特别是,我们证明了GPCRs与细胞外蛋白配体和从对接方法预测的细胞内蛋白效应子（G蛋白）的相互作用，并测试了它们的局限性。本章将帮助研究人员批判性地评估对接方案并预测GPCR复合物的实验可测试结构。
