The research proposed is aimed at establishing novel methodology to probe peptide solution conformation, and supplementing presently available techniques to deduce this information. Specifically, it is proposed to utilize Raman Optical Activity, which is an extension of chiroptical methods into vibrational spectroscopy, and classical solution phase Raman spectroscopy to investigate coupled vibrational states, which are known from previous theoretical and experimental studies to contain conformational information. These spectroscopic techniques, for which instrumental facilities were recently completed in the applicant's laboratory, will be utilized to study specifically designed, water soluble model peptide such that the spectroscopic information can be interpreted directly in terms of conformational information. To achieve this goal, peptides with specific probe groups will be synthesized and studied. The spectroscopic and synthetic efforts will be accompanied by theoretical work aimed at obtaining a detailed understanding of molecular force field necessary to reproduce the observed coupled vibrational states, and at using Raman and Raman Optical Activity intensity calculations to reproduce the observed spectral features quantitatively. Furthermore, molecular dynamics calculations, will be performed to include solvent effects on the molecular conformation. Thus, the proposed research program represents a novel approach, involving instrument development, spectroscopic, synthetic as well as theoretical efforts, to augment present knowledge of peptide solution conformation, and to develope techniques to deduce this information.
NIH ExPorter
NIH ExPorter