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 C-13 nuclear magnetic resonance (NMR) data. A QSDAR model based on 3 spectral bins had an explained variance (r(2)) of 0.80 and a cross-validated variance (q(2)) of 0.78. Another QSDAR model using the 3 atoms from the comparative structurally assigned spectral analysis (CoSASA) of simulated C-13 NMR on a steroid backbone template gave an explained variance (r(2)) of 0.80 and a cross-validated variance (q(2)) 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 C-13 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.