Mesoscopic Model and Free Energy Landscape for Protein-DNA Binding Sites: Analysis of Cyanobacterial Promoters

Tapia-Rojo, R. (Universidad de Zaragoza) ; Mazo, J.J. (Universidad de Zaragoza) ; Hernández, J.Á. ; Peleato, M.L. (Universidad de Zaragoza) ; Fillat, M.F. (Universidad de Zaragoza) ; Falo, F. (Universidad de Zaragoza)

Resumen: 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.

Idioma: Inglés

DOI: 10.1371/journal.pcbi.1003835

Año: 2014

Publicado en: PLoS Computational Biology 10, 10 (2014), e100383 [10 p.]
ISSN: 1553-734X

Factor impacto JCR: 4.62 (2014)

Categ. JCR: MATHEMATICAL & COMPUTATIONAL BIOLOGY rank: 4 / 57 = 0.07 (2014) - Q1 - T1
Categ. JCR: BIOCHEMICAL RESEARCH METHODS rank: 11 / 79 = 0.139 (2014) - Q1 - T1

Financiación: info:eu-repo/grantAgreement/ES/DGA/B18
Financiación: info:eu-repo/grantAgreement/ES/DGA/E19
Financiación: info:eu-repo/grantAgreement/ES/MICINN/BFU2009-07424
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BFU2012-31458
Financiación: info:eu-repo/grantAgreement/ES/MINECO/FIS2011-25167

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Física de la Materia Condensada (Departamento de Física de la Materia Condensada)
Área (Departamento): Bioquímica y Biología Molecular (Departamento de Bioquímica y Biología Molecular y Celular)
Área (Departamento): Fisiología Vegetal (Departamento de Bioquímica y Biología Molecular y Celular)