Comparative Structural Connectivity Spectra Analysis (CoSCoSA) Models of Steroid Binding to the Corticosteroid Binding Globulin.

Abstract

A three-dimensional quantitative spectrometric data-activity relationship (3D-QSDAR) model was developed that is built by combining NMR spectral information with structural information in a 3D-connectivity matrix. The 3D-connectivity matrix is built by displaying all possible carbon-to-carbon connections with their assigned carbon NMR chemical shifts and distances between the carbons. Selected 2D 13C-13C COrrelation SpectroscopY (COSY) (through-bond nearest neighbors) and selected theoretical 2D 13C-13C distance connectivity spectral slices from the 3D-connectivity matrix to produce a relationship among the spectral patterns for 30 steroids binding to corticosteroid binding globulin. We call this technique a comparative structural connectivity spectra analysis (CoSCoSA) modeling. A CoSCoSA principal component linear regression model based on the combination of 13C-13C COSY and 13C-13C distance spectra principal components (PCs) had an r2 of 0.96 and a leave-one-out (LOO) cross-validation q2 of 0.92. A CoS...