G-protein coupled receptors (GPCRs) achieve their functional versatility by adopting various structural conformations defined by different orientations of their characteristic seven transmembrane helices. We predicted inactive and active ensembles of conformations for the dopamine D2 receptor using GEnsemble, which efficiently samples trillions of possible conformations based on different helix orientations. Using the predicted conformational ensembles for inactive and active receptor states, we predicted the binding sites for dopamine, which provides insights into potential receptor activation mechanisms. The binding sites suggest mutagenesis experiments involving the D2 receptor that will provide validation to the binding sites and the activation mechanism proposed based on those sites.

Predicting inactive and active conformations of the dopamine D2 receptor

243rd National Meeting (2012)

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