School of Biomedical Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, England.
School of Chemistry and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, England.
Acta Crystallogr D Struct Biol. 2017 Jun 1;73(Pt 6):534-540. doi: 10.1107/S2059798317004077. Epub 2017 Apr 20.
Recent developments in electron microscopy (EM) have led to a step change in our ability to solve the structures of previously intractable systems, especially membrane proteins and large protein complexes. This has provided new opportunities in the field of structure-based drug design, with a number of high-profile publications resolving the binding sites of small molecules and peptide inhibitors. There are a number of advantages of EM over the more traditional X-ray crystallographic approach, such as resolving different conformational states and permitting the dynamics of a system to be better resolved when not constrained by a crystal lattice. There are still significant challenges to be overcome using an EM approach, not least the speed of structure determination, difficulties with low-occupancy ligands and the modest resolution that is available. However, with the anticipated developments in the field of EM, the potential of EM to become a key tool for structure-based drug design, often complementing X-ray and NMR studies, seems promising.
近年来电子显微镜（EM）技术的发展使得我们解决以前难以处理的系统结构的能力有了质的飞跃，特别是膜蛋白和大型蛋白复合物。这为基于结构的药物设计领域提供了新的机会，有许多备受瞩目的出版物解决了小分子和肽抑制剂的结合位点。与更传统的 X 射线晶体学方法相比，EM 具有许多优势，例如可以解析不同的构象状态，并且当不受晶格约束时，可以更好地解析系统的动力学。使用 EM 方法仍然存在重大挑战，不仅是结构确定的速度，还有低占有率配体的困难和可用的中等分辨率。然而，随着 EM 领域的预期发展，EM 成为基于结构的药物设计的关键工具的潜力似乎很有希望，通常可以补充 X 射线和 NMR 研究。
