Format

Send to

Choose Destination
Methods Enzymol. 2018;610:251-264. doi: 10.1016/bs.mie.2018.09.027. Epub 2018 Oct 15.

Achieving a Good Crystal System for Crystallographic X-Ray Fragment Screening.

Author information

1
Diamond Light Source, Harwell Science and Innovation Campus, Didcot, United Kingdom.
2
Structural Genomics Consortium, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
3
Diamond Light Source, Harwell Science and Innovation Campus, Didcot, United Kingdom; Structural Genomics Consortium, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom; Department of Biochemistry, University of Johannesburg, Aukland Park, South Africa. Electronic address: frank.von-delft@diamond.ac.uk.

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 program 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:

Diamond Light Source; Fragment screening; I04-1; Protein crystallization; Structural genomics consortium; X-ray crystallography; XChem

PMID:
30390801
DOI:
10.1016/bs.mie.2018.09.027
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center