Protein Allostery and Catalysis Beyond Bragg Diffraction

Abstract
The central goal of this project is to understand how protein motion gives rise to function. However, visualizing
proteins in motion is a problem that is inherently difficult in structural biology as it involves signals from many
conformations. To tackle this challenge, we take an interdisciplinary approach. We apply our understanding of
the theory of scattering-based structural methods to develop new computational methods for processing and
interpretating data representing conformational disorder. We have developed methods to extract dynamic infor-
mation from protein crystals that have the potential to animate crystal structures, and we have mapped the
structural interconversions of allosteric and flexible enzymes. In the coming years, we will continue to tackle
fundamental questions about the molecular mechanisms of protein allostery and catalysis, and to do so, we will
expand the scope of our work by integrating cryo-electron microscopy (cryo-EM) with advanced X-ray methods.
Our goals are to: capture correlated motions in allosteric networks, apply our expertise with mathematical de-
composition to the problem of conformational heterogeneity, and (3) probe protein motions that control catalysis.

Grant Number: 5R35GM124847-09
NIH Institute/Center: NIH
Principal Investigator: Nozomi Ando