title: Circular Dichroism of DNA G-Quadruplexes: Combining Modeling and Spectroscopy To Unravel Complex Structures.
abstract: We report on the comparison between the computational and experimental determination of electronic circular dichroism spectra of different guanine quadruplexes obtained from human telomeric sequences. In particular the difference between parallel, antiparallel, and hybrid structures is evidenced, as well as the induction of transitions between the polymorphs depending on the solution environment. Extensive molecular dynamics simulations (MD) are used to probe the conformational space of the different quadruplexes, and subsequently state-of-the-art hybrid quantum mechanics/molecular mechanics (QM/MM) techniques coupled with excitonic semiempirical Hamiltonian are used to simulate the macromolecular induced circular dichroism. The coupling of spectroscopy and molecular simulation allows an efficient one-to-one mapping between structures and optical properties, offering a way to disentangle the rich, yet complicated, quantity of information embedded in circular dichroism spectra. We show that our methodology is robust and efficient and allows us to take into account subtle conformational changes. As such, it could be used as an efficient tool to investigate structural modification upon DNA/drug interactions.
authors.affiliation: Theory-Modeling-Simulation, SRSMC, Université de Lorraine Nancy , Boulevard des Aiguillettes, 54506 Vandoeuvre-lès-Nancy, France.|CNRS, Theory-Modeling-Simulation, SRSMC , Boulevard des Aiguillettes, 54506 Vandoeuvre-lès-Nancy, France.
authors.forename: Hugo
authors.initials: H
authors.lastname: Gattuso
authors.affiliation: Dipartimento di Scienze Biologiche, Chimiche e Farmaceutiche, Universitá di Palermo , Viale delle Scienze, Palermo, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Spinello
authors.affiliation: Dipartimento di Scienze Biologiche, Chimiche e Farmaceutiche, Universitá di Palermo , Viale delle Scienze, Palermo, Italy.|Institute of Inorganic Chemistry, University of Vienna , Währingerstrasse 42, Vienna, Austria.
authors.forename: Alessio
authors.initials: A
authors.lastname: Terenzi
authors.affiliation: Theory-Modeling-Simulation, SRSMC, Université de Lorraine Nancy , Boulevard des Aiguillettes, 54506 Vandoeuvre-lès-Nancy, France.|CNRS, Theory-Modeling-Simulation, SRSMC , Boulevard des Aiguillettes, 54506 Vandoeuvre-lès-Nancy, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Assfeld
authors.affiliation: Dipartimento di Scienze Biologiche, Chimiche e Farmaceutiche, Universitá di Palermo , Viale delle Scienze, Palermo, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Barone
authors.affiliation: Theory-Modeling-Simulation, SRSMC, Université de Lorraine Nancy , Boulevard des Aiguillettes, 54506 Vandoeuvre-lès-Nancy, France.|CNRS, Theory-Modeling-Simulation, SRSMC , Boulevard des Aiguillettes, 54506 Vandoeuvre-lès-Nancy, France.
authors.forename: Antonio
authors.initials: A
authors.lastname: Monari
mesh_terms: D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D006801:Humans; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D011789:Quantum Theory
chemical_list: D004247:DNA