Busato Mirko, Giorgetti Alejandro
Department of Biotechnology, University of Verona, Strada le Grazie 15, 37134 Verona, Italy.
Department of Biotechnology, University of Verona, Strada le Grazie 15, 37134 Verona, Italy; Computational Biomedicine, Institute for Advanced Simulation IAS-5 and Computational Biomedicine, Institute of Neuroscience and Medicine INM-9, Forschungszentrum Jülich, Germany.
Int J Biochem Cell Biol. 2016 Aug;77(Pt B):264-74. doi: 10.1016/j.biocel.2016.04.004. Epub 2016 Apr 19.
Despite the significant efforts and discoveries during the last few years in G protein-coupled receptor (GPCR) expression and crystallization, the receptors with known structures to date are limited only to a small fraction of human GPCRs. The lack of experimental three-dimensional structures of the receptors represents a strong limitation that hampers a deep understanding of their function. Computational techniques are thus a valid alternative strategy to model three-dimensional structures. Indeed, recent advances in the field, together with extraordinary developments in crystallography, in particular due to its ability to capture GPCRs in different activation states, have led to encouraging results in the generation of accurate models. This, prompted the community of modelers to render their methods publicly available through dedicated databases and web-servers. Here, we present an extensive overview on these services, focusing on their advantages, drawbacks and their role in successful applications. Future challenges in the field of GPCR modeling, such as the predictions of long loop regions and the modeling of receptor activation states are presented as well.
尽管在过去几年中，人们在G蛋白偶联受体（GPCR）的表达和结晶方面付出了巨大努力并取得了诸多发现，但迄今为止，具有已知结构的受体仅占人类GPCR的一小部分。缺乏受体的实验性三维结构是一个严重的限制因素，阻碍了对其功能的深入理解。因此，计算技术是一种有效的三维结构建模替代策略。事实上，该领域的最新进展以及晶体学的非凡发展，特别是由于其能够捕获处于不同激活状态的GPCR，在生成精确模型方面取得了令人鼓舞的成果。这促使建模人员群体通过专门的数据库和网络服务器公开其方法。在此，我们对这些服务进行了广泛概述，重点介绍了它们的优点、缺点以及在成功应用中的作用。同时还介绍了GPCR建模领域未来面临的挑战，例如长环区域的预测和受体激活状态的建模。
