We study how drugs change the receptors they bind to using various biochemical and biophysical experimental methods along with molecular dynamics simulations. We then connect these drug induced biophysical changes with drug induced functional outcomes in cell culture (e.g. through measurement of drug induced changes in transcription). Our primary methods are multidimensional protein NMR, fluorine NMR, computational methods, isothermal titration calorimetry, time-resolved FRET, fluoresence polarization, cell culture and transcriptome analysis. We focus on the nuclear hormone receptor family, which is the molecular target of more than 10% of FDA approved drugs. Our work improves the biophysical understanding of how drugs produce effects in this family, this knowledge aids development of new therapies with reduced undesired effects. Current work focues on one member of this family, PPARĪ³, which binds the prescription anti-diabetes drugs pioglitazone (Actos) and rosiglitazone (Avandia).
