Structure‐based prediction of DNA‐binding sites on proteins Using the empirical preference of electrostatic potential and the shape of molecular surfaces

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Abstract
Protein–DNA interactions play an essential role in the genetic activities of life. Many structures of protein–DNA complexes are already known, but the common rules on how and where proteins bind to DNA have not emerged. Many attempts have been made to predict protein–DNA interactions using structural information, but the success rate is still about 80%. We analyzed 63 protein–DNA complexes by focusing our attention on the shape of the molecular surface of the protein and DNA, along with the electrostatic potential on the surface, and constructed a new statistical evaluation function to make predictions of DNA interaction sites on protein molecular surfaces. The shape of the molecular surface was described by a combination of local and global average curvature, which are intended to describe the small convex and concave and the large‐scale concave curvatures of the protein surface preferentially appearing at DNA‐binding sites. Using these structural features, along with the electrostatic potential obtained by solving the Poisson–Boltzmann equation numerically, we have developed prediction schemes with 86% and 96% accuracy for DNA‐binding and non‐DNA‐binding proteins, respectively. Proteins 2004.