SMDC
Small Molecule Discovery Center
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Performing Screens

Investigators are encouraged to review the pertinent scientific literature when considering whether or not a particular target is a good candidate for fragment screening. The guidelines provided here are not comprehensive and are intended only to stimulate thinking about some of the key issues. For x-ray based fragment screening, crystals that diffract to better than 2.5 Å are generally required for unambiguous detection of ligand binding and structure. The small molecule binding site should be unhindered and not of the type that requires a conformational shift prior to ligand binding. For disulfide trapping screens, the protein must be observable by electrospray ionization MS at ≤ 1 µM concentrations. The targeted cysteine residue should be in a surface region where small molecule binding is feasible (e.g., a cavity, crevasse, or known active site) and should have observable conjugation ability with cystamine.

Investigators interested in performing a fragment based screen should contact the SMDC to discuss these issues in more detail. For x-ray screens, the SMDC will provide fragment pools to investigators who will perform the crystallography in their own labs. Disulfide trapping screens will be conducted in the SMDC.