title: Thermally induced protein unfolding probed by isotope-edited IR spectroscopy.
abstract: Infrared (IR) spectroscopy has been widely utilized for the study of protein folding, unfolding, and misfolding processes. We have previously developed a theoretical method for calculating IR spectra of proteins in the amide I region. In this work, we apply this method, in combination with replica-exchange molecular dynamics simulations, to study the equilibrium thermal unfolding transition of the villin headpiece subdomain (HP36). Temperature-dependent IR spectra and spectral densities are calculated. The spectral densities correctly reflect the unfolding conformational changes in the simulation. With the help of isotope labeling, we are able to capture the feature that helix 2 of HP36 loses its secondary structure before global unfolding occurs, in agreement with experiment.
authors.affiliation: Theoretical Chemistry Institute and Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, United States.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: James L
authors.initials: JL
authors.lastname: Skinner
mesh_terms: D007553:Isotope Labeling; D056004:Molecular Dynamics Simulation; D016900:Neurofilament Proteins / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D017433:Protein Structure, Secondary; D058767:Protein Unfolding; D013055:Spectrophotometry, Infrared; D013696:Temperature
chemical_list: D016900:Neurofilament Proteins; D010446:Peptide Fragments; C115223:villin headpiece subdomain peptide