Characterization and prediction of the binding site in DNA-binding proteins: improvement of accuracy by combining residue composition, evolutionary conservation and structural parameters

We present a set of four parameters that in combination can predict DNA-binding residues on protein structures to a high degree of accuracy. These are the number of evolutionary conserved residues (N-cons) and their spatial clustering (rho(e)), hydrogen bond donor capability (D-p) and residue propensity (R-p). We first used these parameters to characterize 130 interfaces in a set of 126 DNA-binding proteins (DBPs). The applicability of these parameters both individually and in combination, to distinguish the true binding region from the rest of the protein surface was then analyzed. R-p shows the best performance identifying the true interface with the top rank in 83% cases. Importantly, we also used the unbound-bound test cases of the protein-DNA docking benchmark to test the efficacy of our method. When applied to the unbound form of the DBPs, R-p can distinguish 86% cases. Finally, we have applied the SVM approach for recognizing the interface region using the above parameters along with the individual amino acid composition as attributes. The accuracy of prediction is 90.5% for the bound structures and 93.6% for the unbound form of the proteins.