Discovery of new heat shock protein 90 inhibitors using virtual co-crystallized pharmacophore generation.

The pharmacophoric features of the virtual cocrystallized protein of 178 Hsp90 proteins were obtained from the protein data bank and explored to generate 1260 pharmacophores evaluated using the decoy list composed of 1022 compounds. Accordingly, 51 pharmacophores were selected with high receiver operating characteristic (ROC) value for further processing. Subsequently, genetic algorithm and multiple linear regression analysis were employed to select an optimal combination of pharmacophoric models and 2D physicochemical descriptors capable of accessing a self-consistent quantitative structure-activity relationship (QSAR) of optimal predictive potential (R = 0.