title: Simulations Meet Experiment to Reveal New Insights into DNA Intrinsic Mechanics.
abstract: The accurate prediction of the structure and dynamics of DNA remains a major challenge in computational biology due to the dearth of precise experimental information on DNA free in solution and limitations in the DNA force-fields underpinning the simulations. A new generation of force-fields has been developed to better represent the sequence-dependent B-DNA intrinsic mechanics, in particular with respect to the BI ↔ BII backbone equilibrium, which is essential to understand the B-DNA properties. Here, the performance of MD simulations with the newly updated force-fields Parmbsc0εζOLI and CHARMM36 was tested against a large ensemble of recent NMR data collected on four DNA dodecamers involved in nucleosome positioning. We find impressive progress towards a coherent, realistic representation of B-DNA in solution, despite residual shortcomings. This improved representation allows new and deeper interpretation of the experimental observables, including regarding the behavior of facing phosphate groups in complementary dinucleotides, and their modulation by the sequence. It also provides the opportunity to extensively revisit and refine the coupling between backbone states and inter base pair parameters, which emerges as a common theme across all the complementary dinucleotides. In sum, the global agreement between simulations and experiment reveals new aspects of intrinsic DNA mechanics, a key component of DNA-protein recognition.
authors.affiliation: LBPA, CNRS, ENS Cachan, Université Paris-Saclay, Cachan, France.|Université Pierre et Marie Curie, Paris, France.
authors.forename: Akli
authors.initials: A
authors.lastname: Ben Imeddourene
authors.affiliation: LBPA, CNRS, ENS Cachan, Université Paris-Saclay, Cachan, France.|LPTM, UMR 8089, Université de Cergy-Pontoise, Cergy-Pontoise, France.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Elbahnsi
authors.affiliation: UMR S665, INSERM, Université Paris Diderot, INTS, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Guéroult
authors.affiliation: LPTM, UMR 8089, Université de Cergy-Pontoise, Cergy-Pontoise, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Oguey
authors.affiliation: Cambridge, United Kingdom.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Foloppe
authors.affiliation: LBPA, CNRS, ENS Cachan, Université Paris-Saclay, Cachan, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Hartmann
mesh_terms: D001483:Base Sequence; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D020539:Sequence Analysis, Protein / Q000379:methods*; D013329:Structure-Activity Relationship