Method for estimating protein-protein binding affinities

摘要

The present invention is directed to a method of predicting the binding affinity between a first molecular entity and a second molecular entity. The method includes (1) calculating the free energy of binding &Dgr;Gbind between the first molecular entity and the second molecular entity according to the equation (17): &Dgr;Gbind=−0.82&Dgr;X+/−+0.064&Dgr;Xc/s−0.6Xsb−0.93Xhb−0.0007Xgap−0.06&Dgr;Xtor−0.36  (17) where X+/− is the total number of exposed charged groups; Xc/s is the total number of exposed hydrophobic groups; Xsb is the total number of salt bridges; Xhb is the total number of hydrogen bonds; Xgap is the gap volume at the interface of the first molecular entity and the second molecular entity; Xtor is the total number of exposed side chain torsions; and where &Dgr; refers to the difference between the bound and unbound states; and (2) evaluating the free energy of binding to predict the binding affinity between the first and second molecular entities.