Protein Dynamics

Funded By:

NSERC Discovery, NSERC CRD, CFI, Ontario MRI, Alzheimer's Society of Canada

Research:

Understanding the Role of Structural 'Disorder' in Protein Function and Pathogenenic Misfolding. The tools of structural biology (X-ray crystallography and Nuclear Magnetic Resonance) have provided us with beautiful, high resolution snapshots of protein structure. However, if proteins were truly as static as they appear in those images, most would be completely non-functional. Motion is a crucial component of how proteins carry out their biological roles and also to how they adopt pathogenic structures in diseases like Alzheimer's and Parkinson's. Research in the Wilson Group centers on the development of new mass spectrometry-based tools to precisely measure the motions that proteins *must* undergo as they catalyze reactions, interact with their binding partners, become modified or undergo structural changes that are linked to disease. Our work is equal parts methods development, where we introduce new mass-spectrometry coupled microfluidic devices to support our work and biochemical, where we acquire new insights into dynamics and protein function. Our major contributions so far have included a new 'epicatalytic' model for the manner in which enzyme motions underlie catalysis (Angewandte Chemie Int. Ed., 51(38), 9666-9669), a new way of identifying allosteric 'hotspots' on enzymes (Lab Chip, DOI: 10.1039/C3LC00007A ) and a microfluidic chip for 'time-resolved' protein dynamics measurements (Anal. Chem., 84(8), 3771-3779).