First-Principles Calculations of Protein Circular Dichroism in the Near Ultraviolet

First-Principles Calculations of Protein Circular Dichroism in the Near Ultraviolet
Received May 13, 2004
Revised Manuscript Received June 24, 2004
Web Release Date: August 6, 2004
David M. Rogers and Jonathan D. Hirst*
ACS Publications
Copyright © 2004 American Chemical Society
School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, U.K.
Electronic transitions in aromatic side chains are responsible for the characteristics of proteins in the near UV. We present the first systematic study of a large number of proteins focused on the accurate calculation of near-UV circular dichroism (CD) spectra. We report new parameter sets derived from ab initio calculations for benzene, phenol, and indole that describe the valence electronic transitions to the 1Lb, 1La, 1Bb, and 1Ba states in the side chains of amino acids phenylalanine, tyrosine, and tryptophan. CD spectra were calculated, using the matrix method with the new side-chain parameters, for 30 proteins whose CD spectra and crystal structures have been made publicly available. The new parameter sets are fully self-consistent and yield near-UV spectra better than those obtained using previous parameter sets. The mean absolute errors for computed wild-type spectra in the near UV are reduced by a factor of ~2. A similiar reduction is found for the near-UV spectra (and difference spectra) of mutants involving aromatic amino acids. Empirical modifications to model vibronic coupling in the side-chain chromophore of phenylalanine offer no overall improvement. Protein CD calculations from first principles coupled with atomic-level modeling enhance the utility and interpretability of CD measurements in the near UV.
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