Semi-Automated Discovery of Structural Elements Controlling GPCR Function

With the advance of hardware and software, it has become routine to obtain trajectories that are tens of microseconds in duration, opening new opportunities for yet more rigorous and reproducible observations on mechanism.

Toward this end, we presented a semi-automated analysis pipeline which operates on featurized simulation data, performs unsupervised clustering, and then identifies which input features are most discriminatory of cluster identity. Application of this pipeline to a large set of G-protein-coupled receptor simulation data shows that it identifies several well-known microswitches. Inspection of these structural elements reveals changes in conformation that are known to accompany functional transitions of the receptor.