Fanelli Francesca
Department of Chemistry, Dulbecco Telethon Institute (DTI), University of Modena and Reggio Emilia, Modena, Italy.
Methods Mol Biol. 2012;914:319-36. doi: 10.1007/978-1-62703-023-6_18.
This article describes a computational strategy aimed at studying the structural communication in G-Protein Coupled Receptors (GPCRs) and G proteins. The strategy relies on comparative Molecular Dynamics (MD) simulations and analyses of wild-type (i.e., reference state) vs. mutated (i.e., perturbed state), or free (i.e., reference state) vs. bound (i.e., perturbed state) forms of a GPCR or a G protein. Bound forms of a GPCR include complexes with small ligands and/or receptor dimers/oligomers, whereas bound forms of heterotrimeric GDP-bound G proteins concern the complex with a GPCR. The computational strategy includes structure prediction of a receptor monomer (in the absence of high-resolution structure), a receptor dimer/oligomer, and a receptor-G protein complex, which constitute the inputs of MD simulations. Finally, the analyses of the MD trajectories are instrumental in inferring the structural/dynamics differences between reference and perturbed states of a GPCR or a G protein. In this respect, focus will be put on the analysis of protein structure networks and communication paths.
本文描述了一种计算策略，旨在研究G蛋白偶联受体（GPCRs）和G蛋白中的结构通讯。该策略依赖于比较分子动力学（MD）模拟以及对野生型（即参考状态）与突变型（即扰动状态），或GPCR或G蛋白的游离形式（即参考状态）与结合形式（即扰动状态）的分析。GPCR的结合形式包括与小分子配体和/或受体二聚体/寡聚体的复合物，而异三聚体GDP结合型G蛋白的结合形式涉及与GPCR的复合物。该计算策略包括受体单体（在缺乏高分辨率结构的情况下）、受体二聚体/寡聚体和受体-G蛋白复合物的结构预测，这些构成了MD模拟的输入。最后，MD轨迹分析有助于推断GPCR或G蛋白参考状态与扰动状态之间的结构/动力学差异。在这方面，将重点分析蛋白质结构网络和通讯路径。
