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计算药物设计在代谢型谷氨酸受体研究中的应用。

Computational Drug Design Applied to the Study of Metabotropic Glutamate Receptors.

机构信息

Laboratori de Medicina Computacional Unitat de Bioestadistica, Facultat de Medicina, Universitat Autónoma de Barcelona, 08193 Bellaterra, Spain.

Computational Chemistry, Janssen Research & Development, Janssen Pharmaceutica N. V., Turnhoutseweg 30, B-2340 Beerse, Belgium.

出版信息

Molecules. 2019 Mar 20;24(6):1098. doi: 10.3390/molecules24061098.

Abstract

Metabotropic glutamate (mGlu) receptors are a family of eight GPCRs that are attractive drug discovery targets to modulate glutamate action and response. Here we review the application of computational methods to the study of this family of receptors. X-ray structures of the extracellular and 7-transmembrane domains have played an important role to enable structure-based modeling approaches, whilst we also discuss the successful application of ligand-based methods. We summarize the literature and highlight the areas where modeling and experiment have delivered important understanding for mGlu receptor drug discovery. Finally, we offer suggestions of future areas of opportunity for computational work.

摘要

代谢型谷氨酸(mGlu)受体是 G 蛋白偶联受体家族的 8 个成员,是调节谷氨酸作用和反应的有吸引力的药物发现靶点。在这里,我们回顾了计算方法在该受体家族研究中的应用。X 射线结构的细胞外和 7 跨膜结构域在基于结构的建模方法中发挥了重要作用,同时我们还讨论了配体的成功应用基于方法。我们总结了文献,并强调了建模和实验在 mGlu 受体药物发现方面提供重要认识的领域。最后,我们为计算工作提出了未来的机会领域。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/870d/6470756/808365e3cda0/molecules-24-01098-g001.jpg

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