Unlocking chemical matter on scale

Fragment-based drug discovery (FBDD) has become an indispensable resource for medicinal chemists in searching for lead candidates. To effectively evaluate fragments, various biophysical methods are applied using a cascade approach as a pre-screening step before determining protein-ligand interactions. This approach has been found to be more effective than direct crystallographic screening based on research.

The use of X-ray crystallography as a primary fragment screening method has been limited by the lack of robust systems for soaking experiments and the solubility challenges of fragments. One of the major obstacles in crystal soaking is the sensitivity of protein crystals, but this can be overcome with the SmartSoak® technology, which stabilizes protein crystals to create high-performance soaking systems without any need for trial-and-error optimization.

Our case studies highlight the advantages of using crystallographic fragment screening as the primary screening method for hit identification. The resulting structural data can then be used to explore chemical space on a large scale using computational methods.

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