title: Mesoscopic model and free energy landscape for protein-DNA binding sites: analysis of cyanobacterial promoters.
abstract: The identification of protein binding sites in promoter sequences is a key problem to understand and control regulation in biochemistry and biotechnological processes. We use a computational method to analyze promoters from a given genome. Our approach is based on a physical model at the mesoscopic level of protein-DNA interaction based on the influence of DNA local conformation on the dynamics of a general particle along the chain. Following the proposed model, the joined dynamics of the protein particle and the DNA portion of interest, only characterized by its base pair sequence, is simulated. The simulation output is analyzed by generating and analyzing the Free Energy Landscape of the system. In order to prove the capacity of prediction of our computational method we have analyzed nine promoters of Anabaena PCC 7120. We are able to identify the transcription starting site of each of the promoters as the most populated macrostate in the dynamics. The developed procedure allows also to characterize promoter macrostates in terms of thermo-statistical magnitudes (free energy and entropy), with valuable biological implications. Our results agree with independent previous experimental results. Thus, our methods appear as a powerful complementary tool for identifying protein binding sites in promoter sequences.
authors.affiliation: Dpto. de Física de la Materia Condensada, Universidad de Zaragoza, Zaragoza, Spain; Institute for Biocomputation and Physics of Complex Systems, Zaragoza, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Tapia-Rojo
authors.affiliation: Dpto. de Física de la Materia Condensada, Universidad de Zaragoza, Zaragoza, Spain; Instituto de Ciencia de Materiales de Aragón, C.S.I.C.-Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Mazo
authors.affiliation: Department of Biochemistry, Midwestern University, Glendale, Arizona, United States of America.
authors.forename: José Ángel
authors.initials: JÁ
authors.lastname: Hernández
authors.affiliation: Institute for Biocomputation and Physics of Complex Systems, Zaragoza, Spain; Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Peleato
authors.affiliation: Institute for Biocomputation and Physics of Complex Systems, Zaragoza, Spain; Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: María F
authors.initials: MF
authors.lastname: Fillat
authors.affiliation: Dpto. de Física de la Materia Condensada, Universidad de Zaragoza, Zaragoza, Spain; Institute for Biocomputation and Physics of Complex Systems, Zaragoza, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Falo
mesh_terms: D001665:Binding Sites; D019295:Computational Biology; D000458:Cyanobacteria / Q000378:metabolism*; D004269:DNA, Bacterial / Q000737:chemistry* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D008957:Models, Genetic; D008958:Models, Molecular; D025341:Principal Component Analysis; D011401:Promoter Regions, Genetic / Q000502:physiology*; D013816:Thermodynamics
chemical_list: D004269:DNA, Bacterial; D004268:DNA-Binding Proteins