Preprint Article Version 1 This version is not peer-reviewed

Achieving a Good Crystal System for Crystallographic X-ray Fragment Screening

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. Preprints 2018, 2018090383 (doi: 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 (doi: 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.

Subject Areas

fragment screening; XChem; protein crystallisation; X-ray crystallography; diamond light source; I04-1; structural genomics consortium

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