There has been a recent and prolific expansion in the number of GPCR crystal structures being solved: in both active and inactive forms and in complex with ligand, with G protein and with each other. Despite this, there is relatively little experimental information about the precise configuration of GPCR oligomers during these different biologically relevant states. While it may be possible to identify the experimental conditions necessary to crystallize a GPCR preferentially in a specific structural conformation, computational approaches afford a potentially more tractable means of describing the probability of formation of receptor dimers and higher order oligomers. Ensemble-based computational methods based on structurally determined dimers, coupled with a computational workflow that uses quantum mechanical methods to analyze the chemical nature of the molecular interactions at a GPCR dimer interface, will generate the reproducible and accurate predictions needed to predict previously unidentified GPCR dimers and to inform future advances in our ability to understand and begin to precisely manipulate GPCR oligomers in biological systems. It may also provide information needed to achieve an increase in the number of experimentally determined oligomeric GPCR structures.

中文翻译：

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GPCR寡聚化的计算预测。

最近解决的GPCR晶体结构数量出现了惊人的增长：呈活性形式和呈非活性形式，并与配体，G蛋白和彼此复合。尽管如此，在这些不同的生物学相关状态下，有关GPCR低聚物的精确构型的实验信息相对较少。虽然有可能确定优先结晶特定结构构象的GPCR所需的实验条件，但计算方法为描述受体二聚体和更高阶低聚物形成的可能性提供了一种可能更易处理的手段。基于结构确定的二聚体的基于集合的计算方法，结合使用量子力学方法分析GPCR二聚体界面分子相互作用的化学性质的计算工作流程，将生成可再现且准确的预测，以预测先前未鉴定的GPCR二聚体，并为我们在理解和理解能力方面的未来发展提供信息开始在生物系统中精确操纵GPCR低聚物。它还可能提供实现实验确定的寡聚GPCR结构数量增加所需的信息。