XChem at Diamond

overview

The XChem Lab at Research Complex is an extension of the XChem initiative, a joint lab spanning Diamond and CMD-Oxford, which developed and runs Diamond’s very successful XChem facility for crystal-based fragment screening. At Research Complex, the XChem Lab is developing methodology in computational and synthetic chemistry to progress XChem hits to credible potency rapidly and cheaply.

The XChem facility allows hundreds of fragment molecules to be screened against crystallised protein targets, much faster than previously but with the high sensitivity of the crystallographic experiment. The readout thus yields directly the high-resolution structural information, i.e. specific configurations and positions of the bound fragments, needed to compute follow-up molecules.

To help analyse this uniquely rich dataset, the team at XChem are building cloud- and HPC-based computational chemistry tools that can both enumerate synthetically and/or logistically accessible follow-up compounds and aid the decision process as to which subset to obtain, from both suppliers and chemist collaborators. In the first instance, we seek to capture and guide best practice in what currently is tedious and requires arcane expertise. This work forms the foundation of the nascent CCP-CompMedChem initiative.

To investigate how to expand the number of compounds that can be accessed practically, the team are exploring how robotic synthesis can be combined with the XChem experiment to allow evaluation of hundreds rather than tens of follow-up compounds. The workhorse is currently the laughably cheap ($4,000) Opentrons liquid-handling robot.

This work aligns exactly with the chemistry theme of the Rosalind Franklin Institute.