Protein

The solution-phase protein motion that is part of a multi-component complex can not always be inferred from the three-dimensional structure. For example, in contrast to the still-life representation of viral capsids in models based on cryo-electron microscopy and X-ray crystallography, these supramolecular protein complexes are highly dynamic in solution. The range and frequency of capsid protein dynamics are poorly understood, despite evidence that the infectivity of animal viruses requires conformational freedom. Protein function is intimately connected to dynamics and therefore knowledge of the frequency, range, and coordination of motion by supramolecular complexes is critical to understanding how they function. Our lab uses viruses as a paradigm for studying protein dynamics in supramolecular complexes. A number of biophysical techniques including time-resolved fluorescence, differential scanning fluorimetry, hydrogen-deuterium exchange, kinetic hydrolysis, and quantitative mass spectrometry, we are determining the free energy and rates of large scale protein motion within viral particles. These are the first quantitative measurements for protein dynamics in megadalton complexes. Selective protein labeling, and quartz crystal microbalance measurements are a few of the additional methods applied to the quantitative analysis of virus particle stability and dynamics. Current projects include the use of Adeno Associated virus in gene therapy and characterization of a novel class of anti-Hepatitis B compounds. 
Graduate students: Navid Movahed and Vamseedhar Rayaprolu. 

Personnel:

Keywords:

Biochemistry, Biophysical, Chemical Biology, Structure