9632124 Hirst This research will provide the theoretical underpinning for the calculation of the circular dichroism (CD) of a protein given its structure. CD is fundamentally an electronic molecular property, and so the first component of the work involves the application of state-of-the-art quantum chemistry methods to characterize the various chromophoric groups in proteins. Once these groups have been modeled, the semi-empirical matrix method for calculating the CD of proteins will be used. Dr. Hirst will use the developed methods to investigate the influences on the CD of helices. In collaboration with Professor Jeffery Kelly at Texas A & M he will investigate the CD of (-sheet peptidomimetics. CD calculations and MD simulations (from Professor Charles Brooks at The Scripps Research Institute) will be used to model the time-evolution of CD during protein folding. %%% Circular dichroism (CD) spectroscopy is a widely used probe of protein structure from early experiments to determine the handedness of (-helices to recent picosecond time-resolved CD measurements of the dissociation of carbonmonoxide from myoglobin. CD is routinely employed to study the structure, the thermodynamics and the kinetics of protein folding. Much of the theoretical basis of the CD of proteins has been established, but the relationship between CD and the detailed structure of proteins has yet to be fully understood. The results of this research, the development of theoretical methods to calculate the circular dichroism spectra of peptides and proteins from simulations, will provide the connection between the atomic-detailed structure of proteins and their CD. ***
