EVALUATING DOCKED COMPLEXES WITH THE HINT EXPONENTIAL FUNCTION AND EMPIRICAL ATOMIC HYDROPHOBICITIES

Methods that predict geometries of ligands binding to receptor molecul es can facilitate ligand discovery and yield information on the factor s governing complementarity. Here, the use of atomic hydrophobicities in evaluating binding modes has been examined with four ligand-recepto r complexes of known structure. In each system, hundreds of hypothetic al binding orientations were generated with DOCK and evaluated using t he HINT (Hydropathic INTeractions) exponential function and atomic hyd rophobic constants. In three of the four systems, the experimental bin ding mode received the best HINT score; in the fourth system, the expe rimental binding mode scored only slightly lower than a similar, appar ently reasonable orientation. The HINT function may be generally usefu l as a scoring method in molecular docking.