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Center for Nonlinear Studies |
In order to understand protein folding, we need to understand both folded and unfolded state structure. One of the key systems for these studies is the 36 residue villin headpiece helical subdomain (HP36) because of its simple topology, small size and fast folding properties. Structures of HP36 have been determined using X-ray crystallography and NMR spectroscopy, with the resulting structures exhibiting clear structural differences. We complement the existing data by using molecular dynamics simulations and experimental double mutant cycles to show that the x-ray structure is the better representation in solution at neutral conditions. Denatured state studies using fragment analysis coupled with relatively low resolution spectroscopic techniques show a small tendency to form locally stabilized structure. Using standard Replica Exchange Molecular Dynamics, our simulations show that the first helix contains the most native-like helical structure of all three helices. Overall, our analysis shows how theoretical and experimental collaborative efforts can help aid in the understanding of the dynamic nature of the folding pathway.
Host: S. Gnanakaran, T-10