A New Method to Predict the Electronic Circular Dichroism Spectra of Proteins

Abstract

Electronic circular dichroism (ECD) is a widely applied tool providing information on the average structure of biomolecules, particularly of proteins. The connection between the ECD spectrum in the far ultraviolet range (175-260 nm) and the secondary structure characteristics of proteins has long been established, and is used to monitor structural re-arrangements during biochemical processes such as (un)folding or binding events. The two main methods to interpret ECD spectra are estimation of the average secondary structure ratios by spectrum deconvolution, or the prediction of the spectrum from a proposed structural model and comparison to the experimental spectrum. However, the ambiguity of spectrum deconvolution, and the computational power required for an accurate spectrum prediction with quantum mechanics limited the quantitative interpretation of protein ECD spectra so far.Here we present a computational method that allows the rapid and accurate prediction of the ECD spectra of proteins using their three-dimensional structure and a set of pre-calculated spectrum components (basis set). We derived several basis sets using the crystal structure and CD spectra of 64 ordered proteins. The basis sets are compatible with established secondary structure classification programs such as DSSP and DISICL. We evaluated the accuracy of the derived basis sets and some of the previously available deconvolution and prediction methods. The results indicate that our method has a comparable accuracy to spectrum deconvolution techniques, while eliminating the ambiguity, and provides a significant (+50%) improvement in accuracy over the available CD spectrum prediction software DichroCalc.