Analysis and prediction of DNA-binding proteins and their binding residues based on composition, sequence and structural information.
BACKGROUND
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.
Ahmad
Shandar
S
Department of Biochemical Science and Engineering, Kyushu Institute of Technology, Fukuoka, Iizuka 820 8502, Japan. shandar@bse.kyutech.ac.jp
Gromiha
M Michael
MM
Sarai
Akinori
A
D000465:Algorithms; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D001185:Artificial Intelligence; D001665:Binding Sites; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000145:classification; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016571:Neural Networks, Computer; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016415:Sequence Alignment / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods*; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000737:chemistry
D000596:Amino Acids; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D004247:DNA