Structure-based drug discovery (SBDD) is an important technique for the pharmaceutical industry which has enabled the generation of a number of drug candidates to treat a wide range of diseases. Structure-guided ligand design is often enabled by X-ray crystallography; however, it is constrained by the limitations inherent to this technique.

In recent years, Cryo-EM has undergone a significant transformation. Practitioners can now consistently generate structures with excellent atomic resolution, even for some challenging targets that cannot be resolved by X-ray crystallography. Therefore, establishing Cryo-EM as a robust orthogonal technique for ligand design. However, one of its classic pitfalls is the poor elucidation of ligands, which impedes the drawing of biological conclusions from the sample and can prevent progression of the candidate into treatment development.

This project will provide Astex with a suite of algorithms and methods that enhance ligand elucidation, unlocking information related to its location, affinity, and pose.