Combining `dry' co‐crystallization and in situ diffraction to facilitate ligand screening by X‐ray crystallography. (1st August 2015)

• Record Type: Journal Article
• Authors: Gelin, Muriel; Delfosse, Vanessa; Allemand, Frédéric; Hoh, François; Sallaz‐Damaz, Yoann; Pirocchi, Michel; Bourguet, William; Ferrer, Jean‐Luc; Labesse, Gilles; Guichou, Jean‐François
• Is Part Of: Acta crystallographica. Volume 71:Part 8(2015:Aug.)
• Page Start: 1777
• Page End: 1787
• Publication Date: 2015-08-01
• Subjects: Biomolecules -- Structure -- Periodicals; Physical biochemistry -- Periodicals; X-ray crystallography -- Periodicals; Crystallography -- Periodicals; 572
• DOI: 10.1107/S1399004715010342
• Languages: English
• ISSNs: 0907-4449

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>X‐ray crystallography is an established technique for ligand screening in fragment‐based drug‐design projects, but the required manual handling steps – soaking crystals with ligand and the subsequent harvesting – are tedious and limit the throughput of the process. Here, an alternative approach is reported: crystallization plates are pre‐coated with potential binders prior to protein crystallization and X‐ray diffraction is performed directly `<italic>in situ</italic>' (or in‐plate). Its performance is demonstrated on distinct and relevant therapeutic targets currently being studied for ligand screening by X‐ray crystallography using either a bending‐magnet beamline or a rotating‐anode generator. The possibility of using DMSO stock solutions of the ligands to be coated opens up a route to screening most chemical libraries.</p> </abstract>