Raman optical activity: An incisive probe of molecular chirality and biomolecular structure

Abstract

The theory, instrumentation and applications of Raman optical activity (ROA), which measures vibrational optical activity by means of a small difference in the intensity of Raman scattering from chiral molecules in right- and left-circularly polarized incident light or, equivalently, a small circularly polarized component in the scattered light, are briefly reviewed. As well as providing the absolute configuration of small chiral molecules, ab initio simulations of observed ROA spectra provide the three-dimensional structure and conformational distribution. The rich ROA spectra of biomolecules in aqueous solution provide detailed structural information including, in the case of proteins, the tertiary fold in addition to secondary structure elements. The many structure-sensitive bands in protein ROA spectra makes them ideal for the application of multivariate analysis methods such as nonlinear mapping to determine structural relationships between different proteins. ROA studies of unfolded and partially folded proteins provide insight into the residual structure in denatured proteins and the aberrant behaviour of proteins responsible for misfolding diseases. It is even possible to measure the ROA spectra of intact viruses, from which information about the fold of the major coat proteins and the structure of the nucleic acid core may be obtained.