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 2H2O 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 2H2O) 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.

[1]  T. Keiderling,et al.  Enhanced sensitivity to conformation in various proteins. Vibrational circular dichroism results. , 1989, Biochemistry.

[2]  T. Keiderling,et al.  Empirical studies of protein secondary structure by vibrational circular dichroism and related techniques. Alpha-lactalbumin and lysozyme as examples. , 1994, Faraday discussions.

[3]  R. Williams.  Protein secondary structure analysis using Raman amide I and amide III spectra. , 1986, Methods in enzymology.

[4]  I. V. van Stokkum,et al.  Estimation of protein secondary structure and error analysis from circular dichroism spectra. , 1990, Analytical biochemistry.

[5]  W C Johnson,et al.  Variable selection method improves the prediction of protein secondary structure from circular dichroism spectra. , 1987, Analytical biochemistry.

[6]  M. Manning,et al.  Underlying assumptions in the estimation of secondary structure content in proteins by circular dichroism spectroscopy--a critical review. , 1989, Journal of pharmaceutical and biomedical analysis.

[7]  T. Keiderling,et al.  Vibrational Circular Dichroism of Proteins in H2O Solution , 1993 .

[8]  W C Johnson,et al.  Extending CD spectra of proteins to 168 nm improves the analysis for secondary structures. , 1992, Analytical biochemistry.

[9]  Vibrational Circular Dichroism , 1981 .

[10]  R. Mitchell,et al.  Determination of protein secondary structure using factor analysis of infrared spectra. , 1990, Biochemistry.

[11]  N. Sreerama,et al.  Protein secondary structure from circular dichroism spectroscopy. Combining variable selection principle and cluster analysis with neural network, ridge regression and self-consistent methods. , 1994, Journal of molecular biology.

[12]  P. Pancoska,et al.  Modified factor analysis of the circular dichroism spectra, applied to a series of cyclodipeptides containing L-proline , 1979 .

[13]  T. Keiderling,et al.  Systematic comparison of statistical analyses of electronic and vibrational circular dichroism for secondary structure prediction of selected proteins. , 1991, Biochemistry.

[14]  Chris Sander,et al.  How to determine protein secondary structure in solution by Raman spectroscopy: practical guide and test case DNase I , 1989 .

[15]  P. Haris,et al.  Protein secondary structure from Fourier transform infrared and/or circular dichroism spectra. , 1993, Analytical biochemistry.

[16]  W. C. Krueger,et al.  Protein secondary structure from Fourier transform infrared spectroscopy: a data base analysis. , 1991, Analytical biochemistry.

[17]  Vibrational circular dichroism , 1976 .

[18]  M. Pézolet,et al.  Determination of the secondary structure content of proteins in aqueous solutions from their amide I and amide II infrared bands. Comparison between classical and partial least-squares methods. , 1990, Biochemistry.

[19]  W. Krueger,et al.  An infrared and circular dichroism combined approach to the analysis of protein secondary structure. , 1991, Analytical biochemistry.

[20]  Edmund R. Malinowski,et al.  Factor Analysis in Chemistry , 1980 .

[21]  T. Keiderling,et al.  Statistical analyses of the vibrational circular dichroism of selected proteins and relationship to secondary structures. , 1991, Biochemistry.

[22]  W. C. Johnson,et al.  Secondary structure of proteins through circular dichroism spectroscopy. , 1988, Annual review of biophysics and biophysical chemistry.

[23]  H. Mantsch,et al.  Determination of protein secondary structure by Fourier transform infrared spectroscopy: a critical assessment. , 1993, Biochemistry.

[24]  H. Susi,et al.  Examination of the secondary structure of proteins by deconvolved FTIR spectra , 1986, Biopolymers.

[25]  T. Keiderling,et al.  Comparison of and limits of accuracy for statistical analyses of vibrational and electronic circular dichroism spectra in terms of correlations to and predictions of protein secondary structure , 1995, Protein science : a publication of the Protein Society.

[26]  W. C. Johnson.  Circular dichroism and its empirical application to biopolymers. , 1985, Methods of biochemical analysis.

[27]  G. Fasman,et al.  Convex constraint analysis: a natural deconvolution of circular dichroism curves of proteins. , 1991, Protein engineering.

[28]  T. Keiderling,et al.  Relationships between secondary structure fractions for globular proteins. Neural network analyses of crystallographic data sets. , 1992, Biochemistry.

[29]  T. Keiderling,et al.  Interconvertibility of Electronic and Vibrational Circular Dichroism Spectra of Proteins: A Test of Principle Using Neural Network Mapping , 1996 .

[30]  S. Provencher,et al.  Estimation of globular protein secondary structure from circular dichroism. , 1981, Biochemistry.

[31]  Johnson Wc,et al.  Information content in the circular dichroism of proteins. , 1981 .

[32]  T. Keiderling,et al.  Vibrational circular dichroism studies of epidermal growth factor and basic fibroblast growth factor. , 1992, Archives of biochemistry and biophysics.

[33]  T. Keiderling,et al.  Quantitative analysis of vibrational circular dichroism spectra of proteins. Problems and perspectives. , 1994, Faraday discussions.

[34]  N. Sreerama,et al.  A self-consistent method for the analysis of protein secondary structure from circular dichroism. , 1993, Analytical biochemistry.

[35]  H. Mantsch,et al.  Resolution enhancement of infrared spectra of biological systems , 1986 .

[36]  M. Pézolet,et al.  On the Spectral Subtraction of Water from the FT-IR Spectra of Aqueous Solutions of Proteins , 1989 .

[37]  W. Kabsch,et al.  Dictionary of protein secondary structure: Pattern recognition of hydrogen‐bonded and geometrical features , 1983, Biopolymers.