title: Role of inter and intramolecular interactions in protein-DNA recognition.
abstract: Protein-DNA recognition plays an essential role in the regulation of gene expression. Regulatory proteins are known to recognize specific DNA sequences directly through atomic contacts between protein and DNA, and/or indirectly through the conformational properties of the DNA. In this work, we have analyzed the specificity of intermolecular interactions by statistical analysis of base-amino acid interactions within protein-DNA complexes as well as the computer simulations of base-amino acid interactions. The specificity of the intramolecular interactions was studied by statistical analysis of the sequence-dependent DNA conformational parameters and the elastic properties of DNA. Systematic comparison of these specificities in a large number of protein-DNA complexes revealed that both intermolecular and intramolecular interactions contribute to the specificity of protein-DNA recognition, and their relative contributions vary depending upon the protein-DNA complex. We demonstrated that combination of the intermolecular and intramolecular energies leads to enhanced specificity and the combined energy could explain experimental data on binding affinity changes caused by base mutations. These results provided new insight into the relationship between specificity and structure in the process of protein-DNA recognition, which would lead to prediction of specific protein-DNA binding sites.
authors.affiliation: Computational Biology Research Center (CBRC), National Institute of Advanced Industrial Science and Technology (AIST), AIST Tokyo Waterfront Bio-IT Research Building, 2-42 Aomi, Koto-ku, Tokyo, 135-0064, Japan. michael-gromiha@aist.go.jp
authors.forename: M Michael
authors.initials: MM
authors.lastname: Gromiha
authors.forename: Joerg G
authors.initials: JG
authors.lastname: Siebers
authors.forename: Samuel
authors.initials: S
authors.lastname: Selvaraj
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Kono
authors.forename: Akinori
authors.initials: A
authors.lastname: Sarai
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016296:Mutagenesis; D009690:Nucleic Acid Conformation; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D011506:Proteins; D004247:DNA