Knowledge of the molecular structures of proteins is increasingly important as we try to understand their function and to modify that function by altering their structures through genetic engineering. One of the important physical tools for studying structure is vibrational (i.e., infrared and Raman) spectroscopy, since it is not limited to the crystalline state (as is x-ray diffraction) or to the solution state (as is high resolution NMR spectroscopy). However, in order to realize its full potential, such spectroscopic studies must progress beyond the band correlation stage to the use of the rigorous methods of normal mode analysis, which permit detailed predictions to be made of spectral frequencies and intensities associated with a given three-dimensional structure. A strong foundation for such approaches has been laid by refining an empirical vibrational force field for the polypeptide chain and applying it to normal mode calculations and the analyses of structure in some peptide and polypeptide systems. Dr. Krimm will now extend this approach to a number of new systems, involving peptide, polypeptide, and disulfide bridge conformations, and use empirical as well as quantum-mechanical force fields to develop molecular mechanics potential functions for accurate spectroscopic predictions as well as molecular dynamics simulations.
