Hosts accepting graduate students and postdocs

Researcher Name: Thompson, Warren (He / Him)

Research Area(s): Methods and Resources, Protein Structure and Folding, Fragment-based-drug-discovery, automated chemistry and algorithmic approaches to drug-design

Affiliation: Diamond Light Source

Country: United Kingdom

Website 

Scientific Interests:

Technologies for rapid and low-cost fragment based drug discovery

Fragment-based methods are now widely popular to identify chemical starting points for drug discovery and chemical biology. Yet a major challenge remains: optimizing these weakly-binding fragments, so they bind potently and become useful hit or even lead molecules, and a general, robust, scalable approach has yet to be established in the field. Our overall ambition is to work out how to achieve bespoke, potent ligands cheaply (<10k per target) and quickly (weeks), something that would transform chemical biology.

Our starting point is to exploit fully the rich structural information from XChem (X-ray crystal-based) fragment screens, to achieve potent compounds in 1 or 2 iterations. Our aim is to routinely access a wide chemical space, through low-cost automated synthesis, driven by AI-based compound design. Our process allows medicinal chemists to routinely synthesize large numbers (100s-1000s) of exploratory molecules rapidly and cheaply, by letting them carefully curate the execution of very diverse synthetic routes.

Current automated chemistry approaches require massive investment (>1M) in hardware and expertise. Instead, to enable lower-cost (<10k) and non-expert access, XChem has developed an automated digitized chemistry ecosystem, Chemist Assisted Robotics (CAR), that combines a cloud-based web-application, digitized chemistry, and automated code generation for reviewing, selecting, and executing the automated synthesis of follow-up compounds.

To enhance follow-up design, we developed the Fragalysis Cloud (http://fragalysis.diamond.ac.uk), which publicly hosts all XChem’s collaborative fragment results, alongside those of a few friendly users. Its scope is deliberately fragment-specific, encompassing analysis, progression, collaboration and dissemination that serves as an input of compound designs into CAR.

What you will get from this fellowship 

At XChem, through automation, computation and engineering, we believe in developing open and accessible tools to drive drug-discovery.

During this fellowship, you will gain drug-discovery pipeline experience – from early-stage chemistry to crystallography – working alongside XChem chemists, computational chemists and crystallographers based at Diamond Light Source. You will be exposed, with hands-on experience, to different fields and technologies that will help develop your understanding and expertise of how the different scientific fields and technologies work together to drive drug-discovery.  

This offer applies to trainees/researchers eligible for the following fellowships

PROBio-Africa Fellowships

Contact:

warren.thompson@diamond.ac.uk