To be native or not to be native, that is the question: Studies of the unfolded state structure of the Villin Headpiece Helical Subdomain

COMP 356

Lauren Wickstrom, lwick442@yahoo.com, Stony Brook University, Biochemistry and Structural Biology, Stony Brook, NY 11794, Daniel P. Raleigh, draleigh@notes.cc.sunysb.edu, Department of Chemistry, State University of New York at Stony Brook, Grad. Chemistry Building Rm. 647, Stony Brook, NY 11794, and Carlos L. Simmerling, carlos.simmerling@sunysb.edu, Department of Chemistry, Stony Brook University, Stony Brook, NY 11790.
In order to understand protein folding, we need to understand both folded and unfolded state structure. The denatured state is more difficult to study experimentally because of its dynamic nature compared to the native state. 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. Experimental and computational work using fragment analysis suggests that there is residual structure in the denatured state of HP36. CD and NMR data for HP21, a peptide containing the first two helices, shows an increased helicity over peptides with the isolated helices, possibly stabilized by tertiary contacts involving aromatic residues. Our current work looks to complement the previous experimental studies of HP21 using Replica Exchange Molecular Dynamics in explicit solvent. Simulations can determine whether these weak interactions in the unfolded state are native-like, which has important implications for understanding the fast folding.
 

Chemical Computing Group Excellence Award
6:00 PM-8:00 PM, Tuesday, August 21, 2007 BCEC -- Ballroom Foyer, Poster

Division of Computers in Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007