LIGAND SCREENING

MSGPP uses the following methods for ligand discovery:

Fragment Cocktail Crystallography (FCC)

~600 fragments are screened by soaking crystals in solutions containing up to 10 compounds of distinct shape.

Thermal Melting Point Shift (T_m)

Compounds which stabilize the folded protein are detected by increases in the protein's melting point, measuring the fluorescent intensity of a dye which increases on binding unfolded protein. ~7000 small molecules are screened in high-throughput fashion.

Virtual screening (VS)

Candidate ligands are selected by several rounds of automated and manual analysis. Two filtered sets are screened: ~1300 in-house compounds; and ~40,000 potentially available compounds from the ZINC virtual collection. We gratefully acknowledge OpenEye Scientific Software, Inc., for providing us with their virtual screening software.