An empirical correlation between secondary structure content and averaged chemical shifts in proteins

Abstract

It is shown that the averaged chemical shift (ACS) of a particular nucleus in the protein backbone empirically correlates well to its secondary structure content (SSC). Chemical shift values of more than 200 proteins obtained from the Biological Magnetic Resonance Bank are used to calculate ACS values, and the SSC is estimated from the corresponding three-dimensional coordinates obtained from the Protein Data Bank. ACS values of (1)H(alpha) show the highest correlation to helical and sheet structure content (correlation coefficient of 0.80 and 0.75, respectively); (1)H(N) exhibits less reliability (0.65 for both sheet and helix), whereas such correlations are poor for the heteronuclei. SSC estimated using this correlation shows a good agreement with the conventional chemical shift index-based approach for a set of proteins that only have chemical shift information but no NMR or x-ray determined three-dimensional structure. These results suggest that even chemical shifts averaged over the entire protein retain significant information about the secondary structure. Thus, the correlation between ACS and SSC can be used to estimate secondary structure content and to monitor large-scale secondary structural changes in protein, as in folding studies.

FIGURE 1

Plots of ACS values versus the secondary structure contents estimated from the three-dimensional structures using the program PROMOTIF. (a) and (b) show the correlation of ¹H_N and ¹⁵N ACS values, respectively, to the percentage of β-sheet structures, whereas (c) and (d) correlate the same ACS values with respect to the percentage of helical structure (sum of α and 3₁₀ helices). Continuous lines represent the linear regression analysis results.

FIGURE 2

Plots of ACS values versus the secondary structure contents estimated from the three-dimensional structures using the program PROMOTIF. (a) and (b) show the correlation ¹H_α and ¹³C_α ACS values, respectively, to the percentage of β-sheet structures, whereas (c) and (d) correlate the same ACS values with respect to the percentage of helical structure (sum of α and 3₁₀ helices). Results of the linear regression analysis are shown by continuous lines.

FIGURE 3

Comparison of helical and sheet content percent calculated using ¹H_α or ¹H_N ACS values to that obtained using a consensus chemical shift index-based method for a set of proteins for which no three-dimensional structures are available. (a) and (b) correspond to the helical content using the ¹H_α and ¹H_N ACS values, respectively, whereas (c) and (d) are the corresponding sheet content using the same ACS values. The dashed lines correspond to a perfect correlation between these two methods.