Structure-activity relationships from molecular similarity matrices.

An alternative method for determining structure-activity correlations is presented. Ligand molecules are described using data matrices derived from the results of N by N (each molecule compared to every other) molecular similarity calculations. The matrices were analyzed using a neural network pattern recognition technique and partial least squares statistics, with the results obtained compared to those achieved using comparative molecular field analysis (CoMFA). The molecular series used in the study comprised 31 steroids. The resultant pattern recognition analysis showed clustering of compounds with high, intermediate, and low affinity into separate regions of the neuron output plots. The cross-validated correlation coefficients obtained from statistical analyses of the matrices against steroid binding data compared well with those achieved using CoMFA. These results show that data matrices derived from molecular similarity calculations can provide the basis for rapid elucidation of both qualitative and quantitative structure-activity relationships.