Serial Crystallography for Structure-Based Drug Discovery.

Autor: Zhu L; Biodesign Center for Applied Structural Discovery, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA; School of Molecular Sciences, Arizona State University, Tempe, AZ 85287, USA., Chen X; Biodesign Center for Applied Structural Discovery, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA; School of Molecular Sciences, Arizona State University, Tempe, AZ 85287, USA., Abola EE; Biodesign Center for Applied Structural Discovery, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA; School of Molecular Sciences, Arizona State University, Tempe, AZ 85287, USA., Jing L; Biodesign Center for Applied Structural Discovery, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA; School of Molecular Sciences, Arizona State University, Tempe, AZ 85287, USA., Liu W; Biodesign Center for Applied Structural Discovery, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA; School of Molecular Sciences, Arizona State University, Tempe, AZ 85287, USA. Electronic address: w.liu@asu.edu.
Jazyk: angličtina
Zdroj: Trends in pharmacological sciences [Trends Pharmacol Sci] 2020 Nov; Vol. 41 (11), pp. 830-839. Date of Electronic Publication: 2020 Sep 16.
DOI: 10.1016/j.tips.2020.08.009
Abstrakt: 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.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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