title: Thermodynamics of DNA: sensitizer recognition. Characterizing binding motifs with all-atom simulations.
abstract: We report the investigation of the thermochemical properties of benzophenone interacting with B-DNA studied by all-atom molecular dynamic simulations. In particular, we determine the binding free energy for two competitive binding modes, minor groove binding and double insertion. Our results allow us to quantitatively resolve for the first time the mode of binding of this paradigmatic photosensitizer, indicating a marked preference for minor groove binding. Furthermore, we have settled a protocol allowing for the determination of binding energies in the case of non-covalent interaction with DNA, in particular, tackling the non-trivial problem of the strong reorganization of the DNA imposing extended statistical sampling. Our contribution paves the way to the systematic determination of the thermochemical properties of drugs or pollutants interacting with DNA.
authors.affiliation: Université de Lorraine - Nancy, Theory-Modeling-Simulation, UMR 7565, Structure et Réactivité des Systémes Moléculaires Complexes (SRSMC), Vandoeuvre-les-Nancy, France. Francois.Dehez@univ-lorraine.fr Antonio.Monari@univ-lorraine.fr and Centre National de la Recherche Scientifique, Theory-Modeling-Simulation, UMR 7565, Structure et Réactivité des Systémes Moléculaires Complexes (SRSMC), Vandoeuvre-les-Nancy, France.
authors.forename: Hugo
authors.initials: H
authors.lastname: Gattuso
authors.affiliation: Laboratoire de Chimie, UMR 5182, Ecole Normale Supérieure de Lyon, Lyon, France. Elise.dumont@ens-lyon.fr.
authors.forename: Elise
authors.initials: E
authors.lastname: Dumont
authors.affiliation: Université de Lorraine - Nancy, Theory-Modeling-Simulation, UMR 7565, Structure et Réactivité des Systémes Moléculaires Complexes (SRSMC), Vandoeuvre-les-Nancy, France. Francois.Dehez@univ-lorraine.fr Antonio.Monari@univ-lorraine.fr and Centre National de la Recherche Scientifique, Theory-Modeling-Simulation, UMR 7565, Structure et Réactivité des Systémes Moléculaires Complexes (SRSMC), Vandoeuvre-les-Nancy, France and Department of Physics, University of Illinois at Urbana-Champaign, 1110 West Green Street, Urbana, Illinois 61801, USA and Laboratoire International Associé, Centre National de la Recherche Scientifique, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Christophe
authors.initials: C
authors.lastname: Chipot
authors.affiliation: Université de Lorraine - Nancy, Theory-Modeling-Simulation, UMR 7565, Structure et Réactivité des Systémes Moléculaires Complexes (SRSMC), Vandoeuvre-les-Nancy, France. Francois.Dehez@univ-lorraine.fr Antonio.Monari@univ-lorraine.fr and Centre National de la Recherche Scientifique, Theory-Modeling-Simulation, UMR 7565, Structure et Réactivité des Systémes Moléculaires Complexes (SRSMC), Vandoeuvre-les-Nancy, France.
authors.forename: Antonio
authors.initials: A
authors.lastname: Monari
authors.affiliation: Université de Lorraine - Nancy, Theory-Modeling-Simulation, UMR 7565, Structure et Réactivité des Systémes Moléculaires Complexes (SRSMC), Vandoeuvre-les-Nancy, France. Francois.Dehez@univ-lorraine.fr Antonio.Monari@univ-lorraine.fr and Centre National de la Recherche Scientifique, Theory-Modeling-Simulation, UMR 7565, Structure et Réactivité des Systémes Moléculaires Complexes (SRSMC), Vandoeuvre-les-Nancy, France and Laboratoire International Associé, Centre National de la Recherche Scientifique, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: François
authors.initials: F
authors.lastname: Dehez
mesh_terms: D000818:Animals; D003198:Computer Simulation; D059371:DNA, B-Form; D006801:Humans; D007364:Intercalating Agents; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D013816:Thermodynamics
chemical_list: D059371:DNA, B-Form; D007364:Intercalating Agents