Analysis and prediction of DNA-binding proteins and their binding residues based on composition, sequence and structural information

摘要

Motivation: Though vitally important to cell function, the mechanism of protein–DNA binding has not yet been completely understood. We therefore analysed the relationship between DNA binding and protein sequence composition, solvent accessibility and secondary structure. Using non-redundant databases of transcription factors and protein–DNA complexes, neural network models were developed to utilize the information present in this relationship to predict DNA-binding proteins and their binding residues. Results: Sequence composition was found to provide sufficient information to predict the probability of its binding to DNA with nearly 69% sensitivity at 64% accuracy for the considered proteins; sequence neighbourhood and solvent accessibility information were sufficient to make binding site predictions with 40% sensitivity at 79% accuracy. Detailed analysis of binding residues shows that some three- and five-residue segments frequently bind to DNA and that solvent accessibility plays a major role in binding. Although, binding behaviour was not associated with any particular secondary structure, there were interesting exceptions at the residue level. Over-representation of some residues in the binding sites was largely lost at the total sequence level, but a different kind of compositional preference was observed in DNA-binding proteins.