An improved PMF scoring function for universally predicting the interactions of a ligand with protein, DNA, and RNA.

An improved potential mean force (PMF) scoring function, named KScore, has been developed by using 23 redefined ligand atom types and 17 protein atom types, as well as 28 newly introduced atom types for nucleic acids (DNA and RNA). Metal ions and water molecules embedded in the binding sites of receptors are considered explicitly by two newly defined atom types. The individual potential terms were devised on the basis of the high-resolution crystal and NMR structures of 2422 protein−ligand complexes, 300 DNA−ligand complexes, and 97 RNA−ligand complexes. The optimized atom pairwise distances and minima of the potentials overcome some of the disadvantages and ambiguities of current PMF potentials; thus, they more reasonably explain the atomic interaction between receptors and ligands. KScore was validated against five test sets of protein−ligand complexes and two sets of nucleic-acid−ligand complexes. The results showed acceptable correlations between KScore scores and experimentally determined binding aff...