Fragment-based screening is now well-established as a powerful approach to early drug ("lead") discovery.
Please acknowledge fundings and resources used as follows:
The XChem facility:
"The authors would like to acknowledge the Diamond Light Source for access to the fragment screening facility XChem, for usage of DSi-Poised library and for beamtime on beamline I04‐1 under proposal LB#####."
The Research Complex at Harwell (RCaH):
For iNEXT-Discovery users:
This work has been supported by iNEXT, grant number PID####, funded by the Horizon 2020 program of the European Union.
For libraries used (except DSi-Poised):
Please use the acknowledgement text which is in each library's page here.
TexRank Crystal Targeting:
Ng, J. T., et al. Using textons to rank crystallisation droplets by the likely presence of crystals. Acta Cryst D, 70, 2701-2718 (2014). https://doi.org/10.1107/S1399004714017581
ECHO Fragment Dispensing:
Collins, P. M., et al. Gentle, fast and effective crystal soaking by acoustic dispensing. Acta Cryst D, 73, 246-255 (2017). https://doi.org/10.1107/S205979831700331X
Cox, O. B., et al. A poised fragment library enables rapid synthetic expansion yielding the first reported inhibitors of PHIP(2), an atypical bromodomain. Chem Sci., 7, 2322-2330 (2016). https://doi.org/10.1039/C5SC03115J
Shifter Crystal Harvesting:
Wright, N. D., et al. The Low-Cost, Semi-automated Shifter Microscope Stage Transforms Speed and Robustness of Manual Protein Crystal Harvesting. Acta Cryst D, 77, 62-74 (2021). https://doi.org/10.1107/S2059798320014114
Krojer, T., et al. The XChem Explorer graphical workflow tool for routine or large-scale protein-ligand structure determination. Acta Cryst D, 73, 267-278 (2017). https://doi.org/10.1107/S2059798316020234
Pearce, N., et al. Partial-occupancy binders identified by the Pan-Dataset Density Analysis method offer new chemical opportunities and reveal cryptic binding sites. Structural Dynamics, 4, 032104 (2017). https://doi.org/10.1063/1.4974176
Pearce, N., et al. A multi-crystal method for extracting obscured crystallographic states from conventionally uninterpretable electron density. Nat. Commun., 8, 15123 (2017). https://doi.org/10.1038/ncomms15123
The XChem pipeline overview
Douangamath, A., et al. Achieving Efficient Fragment Screening at XChem Facility at Diamond Light Source. JoVE journal (2021). https://www.jove.com/t/62414/achieving-efficient-fragment-screening-at-xchem-facility-at-diamond
Diamond Light Source is the UK's national synchrotron science facility, located at the Harwell Science and Innovation Campus in Oxfordshire.
Copyright © 2020 Diamond Light Source
Diamond Light Source Ltd
Harwell Science & Innovation Campus
Diamond Light Source® and the Diamond logo are registered trademarks of Diamond Light Source Ltd
Registered in England and Wales at Diamond House, Harwell Science and Innovation Campus, Didcot, Oxfordshire, OX11 0DE, United Kingdom. Company number: 4375679. VAT number: 287 461 957. Economic Operators Registration and Identification (EORI) number: GB287461957003.