Predictions of secondary structure using statistical analyses of electronic and vibrational circular dichroism and Fourier transform infrared spectra of proteins in H2O

Vibrational circular dichroism (VCD) and Fourier transform IR (FTIR) methods for prediction of protein secondary structure are systematically compared using selective regression analysis. VCD and FTIR spectra over the amide I and II bands of 23 proteins dissolved in H2O were analyzed using the principal component method of factor analysis (PC/FA) and regression fits to fractional components (FC) of secondary structure. Predictive capability was determined by computing structures for proteins sequentially left out of the regression. All possible combinations of PC/FA spectral parameters (coefficients) were used to form a full set of restricted multiple regressions (RMR) of PC/FA coefficients with FC values, both independently for each spectral data set as well as for the VCD and FTIR sets grouped together and with similarly obtained electronic CD (ECD) data. The distribution of predictive error for a set of the best RMR relationships that use a given number of spectral coefficients was used to select the optimal prediction algorithm. Minimum predictive error resulted for a small subset (three to six) of spectral coefficients, which is consistent with our earlier findings using VCD measured for proteins in (H2O)-H-2 and ECD data. Subtracting the average absorption spectrum from all the training set FTIR spectra before analysis yields more variance in the FTIR band shape and improves the predictive ability of the best PC/FA RMR to near that for the VCD. Both methods (FTIR and VCD) using data for proteins in H2O are somewhat better predictors than amide I' (in (H2O)-H-2) VCD alone and, for helix, worse than ECD alone. Combining FTIR and VCD data did not dramatically change the prediction results. Predictions are improved by combining both with ECD data, indicating that the improvement is due to using their very different structural sensitivities. The coupled H2O-based spectral analyses and the mixed amide I' + II VCD plus ECD analysis are comparable for the helix and sheet components, indicating that partial deuteration is not a major source of prediction error. (C) 1996 Academic Press Limited