Distance dependent scoring function for describing protein-ligand intermolecular interactions

A new empirical scoring function has been developed to estimate the binding affinity of a protein-ligand complex with known three-dimensional structure. The scoring function includes a small number of physicochemical descriptors and a large number of quasi-fragmental descriptors. The first group of descriptors is chosen from the following set: (1) the number of close nonbonded contacts, (2) a score for 'metal-atom' interactions, (3) the number of flexible bonds, (4) van der Waals interaction energy, and (5) electrostatic interaction energy. A training set of 288 'protein-ligand' complexes was used to develop the scoring function. The key benefit of this approach is that it reduces the computational complexity while maintaining similar predictive ability to existing methods (average for independent test sets is 2-2.2 kcal/mol). The quasi-fragmental descriptors provide a unique and novel way of accurately representing physical interactions, compared to using physicochemical ones alone.