Membrane proteins are central targets in drug development for a wide range of diseases, yet the role of annular lipids in modulating drug binding and accessibility remains poorly understood. Here, I present high-resolution cryo-EM studies of a drug-bound, temperature-sensitive TRP ion channel, revealing that temperature-dependent remodeling of the annular lipid environment directly regulates drug binding. These lipid rearrangements lead to a repositioning of the drug-binding site, establishing a clear mechanistic link between a physical parameter (temperature), lipid dynamics, and ligand-binding behavior.
This work highlights an underexplored but critical layer of regulation in membrane protein pharmacology, demonstrating how lipid environments can influence drug efficacy and binding modes. These findings have important implications for rational drug design targeting membrane proteins across diverse disease areas. In addition, I will discuss emerging methodological advances in membrane protein isolation and structure determination, enabled in part through collaboration with KACTUS, and outline future directions for integrating lipid biology into drug discovery pipelines.
Key Topics:
- Understand how annular lipids modulate drug binding to membrane proteins and influence binding-site accessibility and dynamics.
- Learn how high-resolution cryo-EM reveals lipid–protein–drug interactions, uncovering mechanisms linking temperature, lipid remodeling, and ligand binding.
- Explore implications for drug discovery, including how lipid environments can be leveraged to improve targeting and design of membrane protein therapeutics.
Presenters
Babatunde Ekundayo
,
PhD
Dr. Babatunde Ekundayo is a Scientist at EPFL specializing in structural biology and cryo-EM, with a focus on drug and therapy development. He has trained and conducted research at leading institutions including Yale, the Friedrich Miescher Institute (FMI), and the University of Geneva. His work spans membrane protein drug discovery, CRISPR-based gene editing, and enzyme engineering, combining high-resolution structural approaches with translational applications. With over a decade of experience and multiple high-impact publications, he brings a multidisciplinary perspective bridging fundamental biology and therapeutic innovation.
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