SPECTRAL SIGNATURES OF STRUCTURAL INHOMOGENEITIES ON FOLDING

这个子项目是众多研究子项目之一

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Short alanine-based peptides that form stable helices in aqueous solution have been the focal point of several experiments aimed at probing the thermodynamics and kinetics of helix formation by means of the temperature dependence of their IR spectra. Alanine-based peptides are highly alpha-helical at low temperature and undergo thermal denaturation. Until now attempts to realistically model temperature-induced changes in their IR spectra upon unfolding have been hampered by a lack of detail regarding structural inhomogeneity and its evolution during denaturation. Recent advances in computational power and algorithms have made possible the calculation of the free-energy landscape of peptides in explicit aqueous solvent. Simulations using the replica-exchange molecular dynamics (REMD) methodology are being performed to sample the ensemble of configurations of a helical peptide over a broad range of temperatures. These ensembles provide insight into how the underlying inhomogeneities due to H-bonding and conformational variability of a folding/unfolding solvated helix are manifested in an IR spectrum.