Episode Description
Dr. Joseph Kim solved cryo-EM structures of mu and kappa opioid receptors bound to the same small molecule — and found it does something different at each one.
In this conversation, Dr. Kim walks through his transition from cryo-electron tomography to GPCR structural biology in Ashish Manglik's lab at UCSF, the strategy behind solving inactive-state receptor structures, and why his favorite GPCR — the galanin receptor — has resisted every small-molecule screen thrown at it.
Key takeaways:
- How one molecule acts as an antagonist at mu and an inverse agonist at kappa
- Why the galanin receptor's peptide binding mode blocks conventional drug discovery
- What it takes to switch fields with no prior biochemistry training
- How building tools on "vanilla" GPCRs prepares you for exotic targets
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