James S. Fraser

Scholar: 2014

Awarded Institution
Assistant Professor
University of California, San Francisco
Department of Bioengineering and Therapeutic Sciences


Research Interests

New Light Sources to Illuminate Protein Conformational Dynamics


Proteins are inherently flexible, but there remains considerable controversy about how protein fluctuations contribute to catalytic functions. This controversy derives, in large part, from the inability of biophysical experiments to directly reveal alternative protein conformations. We are developing new X-ray crystallography experiments to overcome this limitation and visualizing conformations "hidden" in low-levels of electron density. We are using these capabilities to probe how the relative populations of these conformations are affected by mutations and physical perturbations, such as temperature and pressure.

A long term goal is to collect high-resolution, time-resolved data at the revolutionary X-ray Free Electron Laser lightsources. These data will enable us to create dynamic models of protein structures, allowing us to watch molecular movies of proteins as they function. We will use these models to increase the selectivity of small molecules for closely related enzymes and to fine-tune the conformational heterogeneity of artificial enzymes that catalyze new reactions.