The potential use of single‐particle electron microscopy as a tool for structure‐based inhibitor design. Issue 6 (5th June 2017)

• Record Type: Journal Article
• Authors: Rawson, S.; McPhillie, M. J.; Johnson, R. M.; Fishwick, C. W. G.; Muench, S. P.
• Is Part Of: Acta crystallographica. Volume 73:Issue 6(2017)
• Page Start: 534
• Page End: 540
• Publication Date: 2017-06-05
• Subjects: electron microscopy -- structure‐based drug design -- conformational dynamics -- membrane proteins; X-ray crystallography -- Periodicals; Crystallography -- Periodicals; Molecular biology -- Periodicals; Molecular structure -- Periodicals; Biomolecules -- Structure -- Periodicals; Cytology -- Periodicals; Biomolecules -- Structure; Crystallography; Cytology; Molecular biology; Molecular structure; X-ray crystallography; Periodicals; 548
• DOI: 10.1107/S2059798317004077
• Languages: English
• ISSNs: 2059-7983

Abstract

Abstract : Recent developments in electron microscopy have provided new opportunities in the field of structure‐based drug design. This review looks at the challenges that remain and the future prospects for the use of electron microscopy in this area. Abstract : 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.