DNA Deformation Energy as an Indirect Recognition Mechanism in Protein-DNA Interactions

• Published in: IEEE/ACM transactions on computational biology and bioinformatics 2007-01, Vol.4 (1), p.117-125
• Main Authors: Aeling, K.A., Steffen, N.R., Johnson, M., Hatfield, G.W., Lathrop, R.H., Senear, D.F.
• Format: Article
• Language: English
• Subjects: Algorithms; Animals; Base Sequence; Binding Sites; Biochemistry; Bioinformatics; Cellular; Character recognition; Cyclic AMP Receptor Protein - chemistry; Cyclic AMP Receptor Protein - metabolism; Deformable models; Deformation; deformation energy; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA - genetics; DNA - metabolism; DNA bending; DNA Restriction Enzymes - chemistry; DNA Restriction Enzymes - metabolism; DNA, Algal - chemistry; DNA, Algal - genetics; DNA, Algal - metabolism; DNA, Bacterial - chemistry; DNA, Bacterial - genetics; DNA, Bacterial - metabolism; DNA, Protozoan - chemistry; DNA, Protozoan - genetics; DNA, Protozoan - metabolism; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - metabolism; DNA-protein binding; Endodeoxyribonucleases - chemistry; Endodeoxyribonucleases - metabolism; Enzymes; Gene expression; Genomics; Humans; indirect readout; indirect recognition; Integration Host Factors - chemistry; Integration Host Factors - metabolism; Mathematical models; Models, Chemical; Models, Molecular; perceptron learning; Protein Binding; Proteins; Random sequences; Recognition; Serum Response Factor - chemistry; Serum Response Factor - metabolism; Shape; Thermodynamics
• ISSN: 1545-5963; 1557-9964
• DOI: 10.1109/TCBB.2007.1000

Proteins that bind to specific locations in genomic DNA control many basic cellular functions. Proteins detect their binding sites using both direct and indirect recognition mechanisms. Deformation energy, which models the energy required to bend DNA from its native shape to its shape when bound to a protein, has been shown to be an indirect recognition mechanism for one particular protein, integration host factor (IHF). This work extends the analysis of deformation to two other DNA-binding proteins, CRP and SRF, and two endonucleases, I-Crel and I-Ppol. Known binding sites for all five proteins showed statistically significant differences in mean deformation energy as compared to random sequences. Binding sites for the three DNA-binding proteins and one of the endonucleases had mean deformation energies lower than random sequences. Binding sites for I-Ppol had mean deformation energy higher than random sequences. Classifiers that were trained using the deformation energy at each base pair step showed good cross-validated accuracy when classifying unseen sequences as binders or nonbinders. These results support DNA deformation energy as an indirect recognition mechanism across a wider range of DNA-binding proteins. Deformation energy may also have a predictive capacity for the underlying catalytic mechanism of DNA-binding enzymes