The evolutionary geometry of protein dynamics

Twelve protein families, each moving along its first mode. Blue is conserved in place across evolution. Red moves.

We use structural ensembles to find evolutionarily critical modes driving phenotypes of interest. We map and model these residue groups in a variety of protein contexts to derive the evolutionary residuals. Then we close the loop with massively parallel lab assays that correct for evolutionary and structural prediction noise. We use this data to improve lives.

Annotated figure titled Structural ensemble of protein orthologs. A reference structure in blue is overlaid with gray ortholog structures. Four regions of deviation are colored: red for global opening and closing, green for the active-site loop, purple for the helical bundle, yellow for the C-terminal tail. Each is labeled as a mode.

The platform has folded hundreds of thousands of predicted structures across hundreds of protein families. A preprint is in preparation.