SC16: GPCR Structure-Based Drug Discovery

Recent breakthroughs in obtaining high-resolution structures of G Protein-Coupled Receptors (GPCRs) by both X-ray crystallography and Cryo-EM technology, are rapidly impacting the pharmaceutical industry. In this short-course we will review how GPCR structures elucidated to date have informed our current understanding of GPCR function. Examples of how GPCR structural information is being applied to guide rational approaches for GPCR drug discovery will be provided. We will also review how this structural information is complemented by various biophysical techniques that provide information on GPCR dynamics and function. We will discuss new biophysical approaches and share recent examples that illustrate applications for drug discovery.

Topics to be covered:

  • Methodologies for the characterization and crystallization of GPCRs
  • Review of X-ray crystallographic and cryoEM GPCR structures and their lessons
  • Biophysical tools (NMR, fluorescence spectroscopy, EPR, SPR and computational approaches) for observing function-related conformational dynamics of GPCRs
  • Implications of structural knowledge on drug discovery especially related to allosteric modulation by small molecules, ions, and engineered partner proteins


Eddy_MatthewMatthew Eddy, PhD, Assistant Professor, Chemistry, University of Florida

Dr. Matthew Eddy is a physical chemist who specializes in the investigation of the structure and conformational dynamics of membrane proteins, including G Protein-Coupled Receptors, using nuclear magnetic resonance (NMR). Dr. Eddy received his Ph.D. from the the laboratory of Professor Robert Griffin at the Massachusetts Institute of Technology. During his Ph.D., Eddy developed new methodologies for using NMR in the solid state to determine structures of membrane proteins in cellular-like environments. Following his PhD, Dr. Eddy joined the laboratories of Professors Raymond Stevens and Kurt Wüthrich at The Scripps Research Institute and University of Southern California as an American Cancer Society Postdoctoral Fellow, applying an integrative structural biology approach to study human G protein-coupled receptors (GPCRs) and focusing on applications of NMR to understand GPCR allosteric functions. Dr. Eddy has authored or coauthored over 25 peer-reviewed publications in high-profile scientific journals including Cell, JACS, and Structure. Dr. Eddy recently started his own laboratory at the University of Florida, developing new approaches to investigate GPCR structure-function relationships directly in cellular environments.

NEW: Nicolas Villanueva, PhD, Project Scientist, Laboratory of Roger Sunahara, Pharmacology, University of California, San Diego