Protein folding, dynamics and function


My research is focused on protein folding and misfolding, and the role of protein dynamics in function and allosteric regulation. My primary research tools are hydrogen/deuterium exchange, radiolytic footprinting, mass spectrometry, molecular dynamics simulation and small angle x-ray scattering. The biological systems I currently focus on are 1) serpins: a class of metastable protease inhibitors whose unusual biophysical properties render them susceptible to misfolding and polymerization. Serpin misfolding is implicated in a number of inherited diseases including emphysema, thrombosis and early onset dementia. 2) HIV-1 reverse transcriptase: the role of conformational dynamics in inhibition and drug resistance. 3) AAA+ proteases: mechanisms of action and regulation. Additionally, I am part of a collaboration applying novel advanced computational techniques to simulate large conformational changes in all atom detail. More information on work in my group can be found at the Wintrode laboratory website :