Improving the performance of the PLB index for ligand-binding site prediction using dihedral angles and the solvent-accessible surface area.

Protein ligand-binding site prediction is highly important for protein function determination and structure-based drug design. Over the past twenty years, dozens of computational methods have been developed to address this problem. Soga et al. identified ligand cavities based on the preferences of amino acids for the ligand-binding site (RA) and proposed the propensity for ligand binding (PLB) index to rank the cavities on the protein surface. However, we found that residues exhibit different RAs in response to changes in solvent exposure. Furthermore, previous studies have suggested that some dihedral angles of amino acids in specific regions of the Ramachandran plot are preferred at the functional sites of proteins. Based on these discoveries, the amino acid solvent-accessible surface area and dihedral angles were combined with the RA and PLB to obtain two new indexes, multi-factor RA (MF-RA) and multi-factor PLB (MF-PLB). MF-PLB, PLB and other methods were tested using two benchmark databases and two particular ligand-binding sites. The results show that MF-PLB can improve the success rate of PLB for both ligand-bound and ligand-unbound structures, particularly for top choice prediction.