Applications of Cryo-EM in small molecule and biologics drug design. (17th December 2021)

• Record Type: Journal Article
• Authors: Lees, Joshua A.; Dias, Joao M.; Han, Seungil
• Is Part Of: Biochemical Society transactions. Volume 49:Number 6(2021)
• Page Start: 2627
• Page End: 2638
• Publication Date: 2021-12-17
• Subjects: biologics -- cryo-EM -- drug discovery and design -- small molecule -- vaccines; Biochemistry -- Congresses; 572
• DOI: 10.1042/BST20210444
• Languages: English
• ISSNs: 0300-5127

Abstract

Abstract : Electron cryo-microscopy (cryo-EM) is a powerful technique for the structural characterization of biological macromolecules, enabling high-resolution analysis of targets once inaccessible to structural interrogation. In recent years, pharmaceutical companies have begun to utilize cryo-EM for structure-based drug design. Structural analysis of integral membrane proteins, which comprise a large proportion of druggable targets and pose particular challenges for X-ray crystallography, by cryo-EM has enabled insights into important drug target families such as G protein-coupled receptors (GPCRs), ion channels, and solute carrier (SLCs) proteins. Structural characterization of biologics, such as vaccines, viral vectors, and gene therapy agents, has also become significantly more tractable. As a result, cryo-EM has begun to make major impacts in bringing critical therapeutics to market. In this review, we discuss recent instructive examples of impacts from cryo-EM in therapeutics design, focusing largely on its implementation at Pfizer. We also discuss the opportunities afforded by emerging technological advances in cryo-EM, and the prospects for future development of the technique.