title: Ion counting from explicit-solvent simulations and 3D-RISM.
abstract: The ionic atmosphere around nucleic acids remains only partially understood at atomic-level detail. Ion counting (IC) experiments provide a quantitative measure of the ionic atmosphere around nucleic acids and, as such, are a natural route for testing quantitative theoretical approaches. In this article, we replicate IC experiments involving duplex DNA in NaCl(aq) using molecular dynamics (MD) simulation, the three-dimensional reference interaction site model (3D-RISM), and nonlinear Poisson-Boltzmann (NLPB) calculations and test against recent buffer-equilibration atomic emission spectroscopy measurements. Further, we outline the statistical mechanical basis for interpreting IC experiments and clarify the use of specific concentration scales. Near physiological concentrations, MD simulation and 3D-RISM estimates are close to experimental results, but at higher concentrations (>0.7 M), both methods underestimate the number of condensed cations and overestimate the number of excluded anions. The effect of DNA charge on ion and water atmosphere extends 20-25 Å from its surface, yielding layered density profiles. Overall, ion distributions from 3D-RISMs are relatively close to those from corresponding MD simulations, but with less Na(+) binding in grooves and tighter binding to phosphates. NLPB calculations, on the other hand, systematically underestimate the number of condensed cations at almost all concentrations and yield nearly structureless ion distributions that are qualitatively distinct from those generated by both MD simulation and 3D-RISM. These results suggest that MD simulation and 3D-RISM may be further developed to provide quantitative insight into the characterization of the ion atmosphere around nucleic acids and their effect on structure and stability.
authors.affiliation: Department of Chemistry and Chemical Biology and BioMaPS Institute, Rutgers University, Piscataway, New Jersey.
authors.forename: George M
authors.initials: GM
authors.lastname: Giambaşu
authors.affiliation: Department of Chemistry and Chemical Biology and BioMaPS Institute, Rutgers University, Piscataway, New Jersey.
authors.forename: Tyler
authors.initials: T
authors.lastname: Luchko
authors.affiliation: Department of Biochemistry, Stanford University, Stanford, California.
authors.forename: Daniel
authors.initials: D
authors.lastname: Herschlag
authors.affiliation: Department of Chemistry and Chemical Biology and BioMaPS Institute, Rutgers University, Piscataway, New Jersey. Electronic address: york@biomaps.rutgers.edu.
authors.forename: Darrin M
authors.initials: DM
authors.lastname: York
authors.affiliation: Department of Chemistry and Chemical Biology and BioMaPS Institute, Rutgers University, Piscataway, New Jersey. Electronic address: case@biomaps.rutgers.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Case
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012965:Sodium Chloride / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry
chemical_list: D012997:Solvents; D012965:Sodium Chloride; D004247:DNA