Pharmacology, Anatomy & Neurobiology
306A Med Surge II
Summary of Research: Research in Fred Ehlert’s lab focuses on the development of computational methods for the analysis of drug interactions with G protein-coupled receptors (GPCRs). Specifically, we analyze the functional responses of GPCRs and estimate agonist affinity for active and inactive states of the receptor. Our analysis also applies to antagonists, inverse agonists and allosteric ligands. We analyze native signaling pathways in primary cells and tissues and cell lines as well as artificial pathways in cell lines. Unlike the more traditional measurements of observed affinity and efficacy, our estimates of receptor state affinity are unperturbed by the nature of the signaling pathway. Our analysis provides a means of validating conclusions drawn from docking drug molecules onto active and inactive receptor structures in silico. It is also useful for the quantification of agonist signaling through different pathways (agonist bias) and allosteric modulation of pathway selectivity. Finally, our analysis provides a more useful interpretation of structure-activity relationships.