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 dich roism (CD) spectra of proteins occur at 190 nm (associated with the pi pi transition) and 220 nm (associated with the n pi* transition). Th e mean residue ellipticity at 220 nm, [theta](220), is commonly used t o estimate the helix content of a protein. We have assessed first prin ciples CD calculations in the far-UV using 23 different proteins, whos e x-ray crystal structures and CD spectra are known. Using the standar d parameters, derived from semiempirical calculations, for the ground state, n pi and pi pi* electronic states of models of the peptide gro up to describe the relevant charge distributions of the backbone chrom ophore, we find weak correlation between the computed and measured mea n residue ellipticity at 220 nm (Spearman rank correlation coefficient , r = 0.41) and no correlation at 190 nm, Replacing the standard param eters with ones derived from modern quantum chemistry methods (multire ference configuration interaction calculations) gives a significant co rrelation (r = 0.62) between the computed and measured [theta](220), b ut still no correlation at 190 nm. We suggest that further improvement s 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 Physic s.