Free Energy Perturbation (FEP): Another technique in the drug discovery toolbox
Introduction When I first started using CHARMM over 20 years ago as a PhD student, I regularly came across references ...
A recent paper describes the use of Forge and Blaze to discover a series of novel reversible inhibitors of the dual-specificity phosphatase Cdc25. In the prospective study, a field point pharmacophore model was generated using Forge from three structurally diverse, reversible Cdc25 inhibitors and used in field-based virtual screening (Blaze) of 3.7 million commercially available compounds. Seven thiazoles, from the small set of 35 compounds selected for testing, showed reversible inhibition of activity at all three isoforms of Cdc25 (Cdc25A, B and C) at micromolar concentrations. The new series are not structurally related to the initial three starting points, but share their biological properties.
The article is available from the RSC Publishing webpage (DOI: 10.1039/c3md00047h).