Developing 13C NMR quantitative spectrometric data-activity relationship (QSDAR) models of steroid binding to the corticosteroid binding globulin.

We have developed four quantitative spectrometric data-activity relationship (QSDAR) models for 30 steroids binding to corticosteroid binding globulin, based on comparative spectral analysis (CoSA) of simulated 13C nuclear magnetic resonance (NMR) data. A QSDAR model based on 3 spectral bins had an explained variance (r2) of 0.80 and a cross-validated variance (q2) of 0.78. Another QSDAR model using the 3 atoms from the comparative structurally assigned spectral analysis (CoSASA) of simulated 13C NMR on a steroid backbone template gave an explained variance (r2) of 0.80 and a cross-validated variance (q2) of 0.73. Positions 3 and 14 from the steroid backbone template have correlations with the relative binding activity to corticosteroid binding globulin that are greater than 0.52. The explained correlation and cross-validated correlation of these QSDAR models are as good as previously published quantitative structure-activity relationship (QSAR), self-organizing map (SOM) and electrotopological state (E-state) models. One reason that the cross-validated variance of QSDAR models were as good as the other models is that simulated 13C NMR spectral data are more accurate than the errors introduced by the assumptions and approximations used in calculated electrostatic potentials, E-states, HE-states, and the molecular alignment process of QSAR modeling. The QSDAR models developed provide a rapid, simple way to predict the binding activity of a steroid to corticosteroid binding globulin.