The Use of GPCR Structures in Drug Design
The Use of GPCR Structures in Drug Design
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DOI：
10.1016/b978-0-12-385952-5.00011-7
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发表时间：
2011-01-01
期刊：
影响因子：
--
通讯作者：
Marshall, Fiona H.
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文献类型：
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作者：
Congreve, Miles;Langmead, Christopher;Marshall, Fiona H.
基于结构的药物发现通常应用于可溶性靶标，例如蛋白酶和激酶。直到最近，G蛋白偶联受体（GPCR）的多个高分辨率X射线结构才变得可用。在这里，我们审查的技术发展，导致最近过多的GPCR结构。这些包括蛋白质表达和纯化以及稳定受体和使其结晶的技术的发展。我们讨论了来自新结构的研究结果，以了解GPCR的功能和药理学。最后，我们研究了基于结构的药物发现方法的实用性，包括同源建模，虚拟筛选和片段筛选GPCR的背景下，已经从其他目标类别的教训。
Structure-based drug discovery is routinely applied to soluble targets such as proteases and kinases. It is only recently that multiple high-resolution X-ray structures of G protein-coupled receptors (GPCRs) have become available. Here we review the technology developments that have led to the recent plethora of GPCR structures. These include developments in protein expression and purification as well as techniques to stabilize receptors and crystallize them. We discuss the findings derived from the new structures with regard to understanding GPCR function and pharmacology. Finally, we examine the utility of structure-based drug discovery approaches including homology modeling, virtual screening, and fragment screening for GPCRs in the context of what has been learnt from other target classes.