title: How accurate are accurate force-fields for B-DNA?
abstract: Last generation of force-fields are raising expectations on the quality of molecular dynamics (MD) simulations of DNA, as well as to the belief that theoretical models can substitute experimental ones in several cases. However these claims are based on limited benchmarks, where MD simulations have shown the ability to reproduce already existing 'experimental models', which in turn, have an unclear accuracy to represent DNA conformation in solution. In this work we explore the ability of different force-fields to predict the structure of two new B-DNA dodecamers, determined herein by means of 1H nuclear magnetic resonance (NMR). The study allowed us to check directly for experimental NMR observables on duplexes previously not solved, and also to assess the reliability of 'experimental structures'. We observed that technical details in the annealing procedures can induce non-negligible local changes in the final structures. We also found that while not all theoretical simulations are equally reliable, those obtained using last generation of AMBER force-fields (BSC1 and BSC0OL15) show predictive power in the multi-microsecond timescale and can be safely used to reproduce global structure of DNA duplexes and fine sequence-dependent details.
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, 08028 Barcelona, Spain.|Joint BSC-IRB Program in Computational Biology, Institute for Research in Biomedicine, Baldiri Reixac 10-12, 08028 Barcelona, Spain.
authors.forename: Pablo D
authors.initials: PD
authors.lastname: Dans
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, 08028 Barcelona, Spain.|Joint BSC-IRB Program in Computational Biology, Institute for Research in Biomedicine, Baldiri Reixac 10-12, 08028 Barcelona, Spain.
authors.forename: Ivan
authors.initials: I
authors.lastname: Ivani
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, 08028 Barcelona, Spain.|Joint BSC-IRB Program in Computational Biology, Institute for Research in Biomedicine, Baldiri Reixac 10-12, 08028 Barcelona, Spain.
authors.forename: Adam
authors.initials: A
authors.lastname: Hospital
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, 08028 Barcelona, Spain.|Joint BSC-IRB Program in Computational Biology, Institute for Research in Biomedicine, Baldiri Reixac 10-12, 08028 Barcelona, Spain.|Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW Cambridge, UK.
authors.forename: Guillem
authors.initials: G
authors.lastname: Portella
authors.affiliation: Instituto Química Física Rocasolano. Consejo Superior de Investigaciones Científicas (CSIC), Serrano 119, 28006 Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: González
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, 08028 Barcelona, Spain.|Joint BSC-IRB Program in Computational Biology, Institute for Research in Biomedicine, Baldiri Reixac 10-12, 08028 Barcelona, Spain.|Department of Biochemistry and Biomedicine, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain.
authors.forename: Modesto
authors.initials: M
authors.lastname: Orozco
mesh_terms: D001483:Base Sequence; D018360:Crystallography, X-Ray; D059371:DNA, B-Form / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation
chemical_list: D059371:DNA, B-Form