TCBG Seminar

Elucidation of G Protein-Coupled Receptor Activation via Data-Driven Modeling

Professor Lucie Delemotte
Applied Physics
KTH Royal Institute of Technology
Stockholm, Sweden

Monday, March 29, 2021
11:00 am (CT)
Zoom webinar recording


Ligand binding stabilizes different G protein-coupled receptor states via a complex allosteric process that is not completely understood. Using enhanced sampling molecular dynamics simulations, we derive free energy landscapes describing activation of the β2 adrenergic receptor bound to ligands with different efficacy profiles. These reveal that the ligands modulate the conformational ensemble of the receptor by tuning protein microswitches. The distribution of these molecular switches is furthermore predictive of cyclic adenosine monophosphate signaling responses. Dimensionality reduction and examining the output of classifiers further enables us to propose a model of regulation of the conformational ensemble by different ligands.

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