4D-QSPR Analysis and Virtual Screening of Calcite Growth Inhibitor Libraries

Abstract

A training set of 35 compounds whose calcite growth inhibition potencies were measured was used to construct a 4D-QSPR model. A site-specific binding pattern of atom types in space, that is a pharmacophore, consisting of six interaction sites between the inhibitors and the surface to which they bind was identified and represented by the 4D-QSPR model. Three of these pharmacophore sites dominate the 4D-QSPR model. One pharmacophore site indicates that its occupancy by any inhibitor atom decreases inhibition potency, suggesting this region of space is occupied by the binding surface. A second pharmacophore site involves an oxygen of a PO3H2 group, which is common to all compounds of the training set, hydrogen bonding to the surface. The third major pharmacophore site identifies a nonpolar region of space as being favorable to inhibition potency. A virtual library of 20 analogues to the training set was evaluated by using the 4D-QSPR model as a virtual high throughput screen, VHTS. Seven of the compounds in ...