4D-QSPR analysis and virtual screening of calcite growth inhibitor libraries

A training set of 35 compounds whose calcite growth inhibition potencies we re 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 pharma cophore sites dominate the 4D-QSPR model. One pharmacophore site indicates that its occupancy by any inhibitor atom decreases inhibition potency, sugg esting this region of space is occupied by the binding surface. A second ph armacophore site involves an oxygen of a PO3H2 group, which is common to al l compounds of the training set, hydrogen bonding to the surface. The third major pharmacophore site identifies a nonpolar region of space as being fa vorable to inhibition potency. A virtual library of 20 analogues to the tra ining set was evaluated by using the 4D-QSPR model as a virtual high throug hput screen, VHTS. Seven of the compounds in the virtual library are predic ted to be better calcite growth inhibitors than the most potent inhibitor o f the training set.