Improving protein circular dichroism calculations in the far-ultraviolet through reparametrizing the amide chromophore

The two most prominent peaks in the far-ultraviolet (UV) circular dichroism (CD) spectra of proteins occur at 190 nm (associated with the pi pi* transition) and 220 nm (associated with the n pi* transition). The mean residue ellipticity at 220 nm, [theta](220), is commonly used to estimate the helix content of a protein. We have assessed first principles CD calculations in the far-UV using 23 different proteins, whose x-ray crystal structures and CD spectra are known. Using the standard parameters, derived from semiempirical calculations, for the ground state, n pi* and pi pi* electronic states of models of the peptide group to describe the relevant charge distributions of the backbone chromophore, we find weak correlation between the computed and measured mean residue ellipticity at 220 nm (Spearman rank correlation coefficient, r = 0.41) and no correlation at 190 nm, Replacing the standard parameters with ones derived from modern quantum chemistry methods (multireference configuration interaction calculations) gives a significant correlation (r = 0.62) between the computed and measured [theta](220), but still no correlation at 190 nm. We suggest that further improvements might be expected from a parametrization of the higher energy slates of the backbone chromophore, and from a more modem parametrization of side-chain chromophoric groups. (C) 1998 American Institute of Physics.