Protein molecules display a variety of conformational fluctuations, over a broad range of timescales, that are often fundamental to their normal function and roles in disease. Protein dynamics underlie such diverse molecular processes as enzyme catalysis, drug transport, motor protein function, and signal transduction. Moreover, a significant fraction of human proteins are so dynamic that they do not fold into a single well-defined state. This behavior is challenging to characterize and control by conventional structural biology and drug design approaches.
The Nath lab focuses on understanding the relationship between protein dynamics and normal function or pathological dysfunction, and on developing new tools to study and ultimately modulate functionally relevant conformational fluctuations. We use a broad range of experimental and theoretical approaches from biochemistry, biophysics and pharmacology, including, in particular, single-molecule fluorescence spectroscopy and computational simulations. Systems of interest include the Glutathione-S-Transferase enzyme superfamily (involved in drug metabolism and the response to oxidative stress) and the intrinsically disordered protein Tau (implicated in Alzheimer’s disease and pathology due to traumatic brain injury).