Identifying DNA-binding proteins using structural motifs and the electrostatic potential

Robust methods to detect DNA-binding proteins from structures of unknown function are important for structural biology. This paper describes a method for identifying such proteins that (i) have a solvent accessible structural motif necessary for DNA-binding and (ii) a positive electrostatic potential in the region of the binding region. We focus on three structural motifs: helix–turn-helix (HTH), helix– hairpin–helix (HhH) and helix–loop–helix (HLH). We find that the combination of these variables detect 78 % of proteins with an HTH motif, which is a substan-tial improvement over previous work based purely on structural templates and is comparable to more complex methods of identifying DNA-binding pro-teins. Similar true positive fractions are achieved for the HhH and HLH motifs. We see evidence of wide evolutionary diversity for DNA-binding proteins with an HTH motif, and much smaller diversity for those with an HhH or HLH motif