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.
Biochemistry, Biophysical, Chemical Biology, Structure