B.Sc. (University of Guelph Biophysics 1996)
Ph.D. (University of Toronto Biochemistry 2003)
Office: Pulp & Paper 102
Email: Anthony.Mittermaier [at] McGill.CA
Lab: Pulp & Paper 304
Lab Phone: 514-398-2093
Flexibility is critical to the biological activity of proteins. Conformational fluctuations alter the spatial arrangement of functionally important groups and stabilize operative states, and thus a knowledge of protein dynamics is essential for the rational design of drugs, novel catalysts and nanoscale devices. The major goals of our research are (1) to develop an understanding of how the primary amino-acid sequence of a protein determines its dynamic properties, and (2) to establish rigorous links between structural mobility at the microscopic level and macroscopic functional activity.
The central technique employed by our group is nuclear magnetic resonance (NMR) spectroscopy. NMR provides detailed structural information for protein molecules, and can quantify motions that occur on timescales ranging from picoseconds to hours with atomic precision. In order to compare dynamics data with measures of activity, we use isothermal titration calorimetry to characterize protein function, in particular the thermodynamics of molecular recognition and catalysis. Molecular biology and mutagenesis methods are applied to directly probe the relationship between protein sequence, dynamics, and function.
Specific systems of interest are:
* disorder/order transitions and DNA binding of homeodomains
* ligand access to a buried cavity in porcine odourant-binding protein
* active-site flexibility and catalysis in staphylococcal nuclease
* ligand discrimination by the Abl SH3 domain
* development and testing of models relating NMR dynamics parameters to calorimetric entropy measurements