Serial Crystallography for Structure-Based Drug Discovery. Trends Pharmacol Sci 2020 Nov;41(11):830-839
Date
09/21/2020Pubmed ID
32950259Pubmed Central ID
PMC7572805DOI
10.1016/j.tips.2020.08.009Scopus ID
2-s2.0-85091103704 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
Rational drug discovery has greatly accelerated the development of safer and more efficacious therapeutics, assisted significantly by insights from experimentally determined 3D structures of ligands in complex with their targets. Serial crystallography (SX) with X-ray free-electron lasers has enabled structural determination using micrometer- or nanometer-size crystals. This technology, applied in the past decade to solve structures of notoriously difficult-to-study drug targets at room temperature, has now been adapted for use in synchrotron radiation facilities. Ultrashort time scales allow time-resolved characterization of dynamic structural changes and pave the road to study the molecular mechanisms by 'molecular movie.' This article summarizes the latest progress in SX technology and deliberates its demanding applications in future structure-based drug discovery.
Author List
Zhu L, Chen X, Abola EE, Jing L, Liu WAuthors
Wei Liu PhD Associate Professor in the Pharmacology and Toxicology department at Medical College of WisconsinLan Zhu PhD Assistant Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Crystallography, X-RayDrug Discovery
Humans
Lasers
Protein Conformation
Receptors, G-Protein-Coupled
Structure-Activity Relationship
Synchrotrons
