title: Structural and energetic origins of sequence-specific DNA bending: Monte Carlo simulations of papillomavirus E2-DNA binding sites.
abstract: DNA bending is an important structural feature for indirect readout in protein-DNA recognition. The binding of papillomavirus E2 transcription factors to their DNA binding sites is associated with DNA bending, providing an attractive model system to study the origins of sequence-specific DNA bending. The consensus E2 target is of the general form ACCGN(4)CGGT with a variable four base pair region. We applied a new all-atom Monte Carlo (MC) algorithm that combines effective sampling with fast conformational equilibration. The resulting MC ensembles resemble the corresponding high-resolution crystal structures very well. Distinct bending is observed for the E2-DNA binding site with a central AATT linker in contrast to an essentially straight DNA with a central ACGT linker. Contributions of specific base pair steps to the overall bending are shown in terms of local structural parameters. The analysis of conformational substates provides new insights into the energetic origins of intrinsic DNA bending.
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel. mail@remo-rohs.de
authors.forename: Remo
authors.initials: R
authors.lastname: Rohs
authors.forename: Heinz
authors.initials: H
authors.lastname: Sklenar
authors.forename: Zippora
authors.initials: Z
authors.lastname: Shakked
mesh_terms: D000465:Algorithms; D020029:Base Pairing; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004279:DNA, Viral / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009010:Monte Carlo Method; D009690:Nucleic Acid Conformation; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004279:DNA, Viral; D009856:Oncogene Proteins, Viral; D014157:Transcription Factors; C069102:oncogene protein E2, Human papillomavirus type 18