Version 1
: Received: 19 September 2018 / Approved: 19 September 2018 / Online: 19 September 2018 (11:37:41 CEST)
How to cite:
Collins, P. M.; Douangamath, A.; Talon, R.; Dias, A.; Brandão-Neto, J.; Krojer, T.; von Delft, F. Achieving a Good Crystal System for Crystallographic X-ray Fragment Screening. Preprints2018, 2018090383. https://doi.org/10.20944/preprints201809.0383.v1
Collins, P. M.; Douangamath, A.; Talon, R.; Dias, A.; Brandão-Neto, J.; Krojer, T.; von Delft, F. Achieving a Good Crystal System for Crystallographic X-ray Fragment Screening. Preprints 2018, 2018090383. https://doi.org/10.20944/preprints201809.0383.v1
Collins, P. M.; Douangamath, A.; Talon, R.; Dias, A.; Brandão-Neto, J.; Krojer, T.; von Delft, F. Achieving a Good Crystal System for Crystallographic X-ray Fragment Screening. Preprints2018, 2018090383. https://doi.org/10.20944/preprints201809.0383.v1
APA Style
Collins, P. M., Douangamath, A., Talon, R., Dias, A., Brandão-Neto, J., Krojer, T., & von Delft, F. (2018). Achieving a Good Crystal System for Crystallographic X-ray Fragment Screening. Preprints. https://doi.org/10.20944/preprints201809.0383.v1
Chicago/Turabian Style
Collins, P. M., Tobias Krojer and Frank von Delft. 2018 "Achieving a Good Crystal System for Crystallographic X-ray Fragment Screening" Preprints. https://doi.org/10.20944/preprints201809.0383.v1
Abstract
The XChem facility at Diamond Light Source offers fragment screening by X-ray crystallography as a general access user program. The main advantage of X-ray crystallography as a primary fragment screen is that it yields directly the location and pose of the fragment hits, whether within pockets of interest or merely on surface sites: this is the key information for structure-based design and for enabling synthesis of follow-up molecules. Extensive streamlining of the screening experiment at XChem has engendered a very active user programme that is generating large amounts of data: in 2017, 36 academic and industry groups generated 35,000 datasets of uniquely soaked crystals. It has also generated a large number of learnings concerning the main remaining bottleneck, namely obtaining a suitable crystal system that will support a successful fragment screen. Here we discuss the practicalities of generating screen-ready crystals that have useful electron density maps, and how to ensure they will be successfully reproduced and usable at a facility outside the home lab.
Keywords
fragment screening; XChem; protein crystallisation; X-ray crystallography; diamond light source; I04-1; structural genomics consortium
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.