Simbios Talk by Adam Godzik, University of California San Diego, December 13, 2006

Title: Evolutionary flexibility in protein structures – what physics can learn from biology

With close to 40,000 protein structures deposited in PDB we know that there are at least 1000+ folds, and we have dozens of examples of structures for most. We understand the forces that shape protein structures – but with all that we are still not able to reliably predict protein structure from sequence, or even predict how structures change upon mutations.

In my group we are exploring a heuristic approach to this problem. We use novel mathematical tools to compare protein structures and to describe and classify differences between them. We hope that would allow us to find empirical rules describing fold-specific rules of structural divergence in protein families. Preliminary results suggests that such divergence is indeed not random, but is confined to small subspace of the overall conformational space. With right (generalized) coordinates things may well be simpler that we thought. We now develop tools to use these insights in atomic level simulations, with applications to docking, molecular replacement and protein homology modeling.