2014-01-28 23:01:07 - Fiona Marshall, Chief Scientific Officer at Heptares Therapeutics, will present on “Structure-Based Drug Discovery Applied to GPCRs” at the GPCR Structure, Function and Drug Discovery Conference, to be held May 22-23, 2014 in Cambridge, MA.
The recent availability of X-ray protein-ligand structures for a diversity of G protein-coupled receptors (GPCRs) in multiple conformations (both inactive and active) enables protein structure-based drug design (SBDD) approaches, which have been highly successful with soluble targets, to now be used to discover better GPCR drug candidates.
Dr. Marshall will present insights from these new ligand-receptor complexes with a variety of computational methods, including water energetics, which are used to analyze druggability and drive design. For instance, StaR® proteins have been thermostabilized in a chosen conformational state by the introduction of a small number of point mutations. These proteins are stable in detergent and can be readily removed from their native cell membranes and purified, thus enabling SBDD approaches. StaR proteins
can be used for biophysical screening techniques, fragment screening, and crystallization to yield X-ray structures with both potent and weak ligands.
Dr. Marshall will also share SBDD examples that will yield clinical candidates with better properties and selectivity and progress with structure- and fragment-based methods for Class B receptors.
For more information about the conference, please visit www.gtcbio.com/gpcr.