title: DNA deformation energy as an indirect recognition mechanism in protein-DNA interactions.
abstract: 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-CreI and I-PpoI. 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-PpoI 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.
authors.affiliation: Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, 92697-3425, USA. kaeling@uci.edu
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Aeling
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Steffen
authors.forename: Matthew
authors.initials: M
authors.lastname: Johnson
authors.forename: G Wesley
authors.initials: GW
authors.lastname: Hatfield
authors.forename: Richard H
authors.initials: RH
authors.lastname: Lathrop
authors.forename: Donald F
authors.initials: DF
authors.lastname: Senear
mesh_terms: D000465:Algorithms; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002373:Cyclic AMP Receptor Protein / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004262:DNA Restriction Enzymes / Q000737:chemistry / Q000378:metabolism; D048028:DNA, Algal / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D034982:Integration Host Factors / Q000737:chemistry / Q000378:metabolism; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D026362:Serum Response Factor / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D002373:Cyclic AMP Receptor Protein; D048028:DNA, Algal; D004269:DNA, Bacterial; D016054:DNA, Protozoan; D004268:DNA-Binding Proteins; D034982:Integration Host Factors; D026362:Serum Response Factor; D004247:DNA; D004706:Endodeoxyribonucleases; C064579:I-Ppo endonuclease; D004262:DNA Restriction Enzymes; C048901:endodeoxyribonuclease CreI