Harnessing cryo-EM to investigate GPCR structure and discover new medicines

Originally aired: Wednesday, 27 May 2020

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Overview

G protein–coupled receptors (GPCRs) are an important family of drug targets—about one-third of all U.S. Food and Drug Administration-approved drugs target the 800 GPCR family members. Despite many success stories, there are still a significant number of GPCR-targeting drugs that never leave the preclinical testing stage. Rational drug design at both orthosteric and allosteric binding sites hold the key for exploiting GPCR targets in full. Over the last 10 years, substantial progress has been made in the structural biology of GPCRs, facilitated by structure-based drug design (SBDD) approaches. Recent progress in the field of cryo-electron microscopy (cryo-EM) has enabled researchers to consistently image proteins at resolutions in the 2.5-Å range, leading to greater biological insights into ligand recognition and GPCR activation. Together, these advances point to GPCR SBDD becoming the new normal for delivering first-in-class and best-in-class drugs.

This webinar will be presented by Matthew Belousoff from the Monash Institute of Pharmaceutical Sciences and Stacey Southall from Sosei Heptares, who will share their use of cryo-EM and how it fits into both the discovery and pharmaceutical side of GPCR research.

During this webinar, the speakers will:

  • Describe the activation of receptor complexes and the presence of multiple dynamic states
  • Discuss the advantages of Sosei Heptares’ StaR (Stabilized Receptor) technology for cryo-EM structures
  • Showcase incorporating single-particle analysis into industrial SBDD workflows.

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Presenters

Presenter
Speaker: Matthew Belousoff, Ph.D.
Monash University
Clayton, Australia
View Bio
Presenter
Speaker: Stacey Southall, Ph.D.
Sosei Heptares
Cambridge, UK
View Bio
Presenter
Moderator: Jackie Oberst, Ph.D
Science/AAAS
Washington, DC
View Moderator Biography