Acknowledgement and references

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#####."

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.

Accelerating Drug Discovery With High-Throughput Crystallographic Fragment Screening and Structural Enablement:

Fearon, D., et al., Accelerating Drug Discovery With High-Throughput Crystallographic Fragment Screening and Structural Enablement., Applied Research (2024), https://doi.org/10.1002/appl.202400192

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

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

Fragment Libraries:

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

XChem Explorer:

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

PanDDA:

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