Samuel Krimm of the University of Michigan is supported by an award from the Theoretical and Computational Chemistry program to develop theoretical methods to strengthen the ability of IR and Raman techniques to provide strong conclusions about conformational structures of peptides and proteins, particularly in aqueous solution. In particular, a hitherto unused non-amide frequency has been discovered that is conformation sensitive, and the aim of this research is to establish all of the expected correlations between structure and spectrum that will enable the use of this band in the determination of peptide and protein structure. The theoretical work consists of quantum mechanical calculations of representative conformations of di-, tri-, tetra-, and penta-peptides to firmly establish the vibrational frequencies to be associated with C(alpha)D(alpha) groups in various positions and structural states, both in isolated molecules and ones to which water molecules are hydrogen bonded to the peptide groups. Factors which are being examined include: a) influence of the amino acid side chain; b) influence of charged end groups; c) influence of position in chain; d) kinds of conformations; and e) effect of the neighboring (i.e. not directly hydrogen-bonded) water medium. The development of this new tool for determining peptide conformation is having a very broad impact across many areas of the biochemical and biophysical sciences.
