title: Evaluation of ion binding to DNA duplexes using a size-modified Poisson-Boltzmann theory.
abstract: Poisson-Boltzmann (PB) theory is among the most widely applied electrostatic theories in biological and chemical science. Despite its reasonable success in explaining a wide variety of phenomena, it fails to incorporate two basic physical effects, ion size and ion-ion correlations, into its theoretical treatment. Recent experimental work has shown significant deviations from PB theory in competitive monovalent and divalent ion binding to a DNA duplex. The experimental data for monovalent binding are consistent with a hypothesis that attributes these deviations to counterion size. To model the observed differences, we have generalized an existing size-modified Poisson-Boltzmann (SMPB) theory and developed a new numerical implementation that solves the generalized theory around complex, atomistic representations of biological molecules. The results of our analysis show that good agreement to data at monovalent ion concentrations up to approximately 150 mM can be attained by adjusting the ion-size parameters in the new size-modified theory. SMPB calculations employing calibrated ion-size parameters predict experimental observations for other nucleic acid structures and salt conditions, demonstrating that the theory is predictive. We are, however, unable to model the observed deviations in the divalent competition data with a theory that only accounts for size but neglects ion-ion correlations, highlighting the need for theoretical descriptions that further incorporate ion-ion correlations. The accompanying numerical solver has been released publicly, providing the general scientific community the ability to compute SMPB solutions around a variety of different biological structures with only modest computational resources.
authors.affiliation: Department of Applied Physics, Stanford University, California, USA.
authors.forename: Vincent B
authors.initials: VB
authors.lastname: Chu
authors.forename: Yu
authors.initials: Y
authors.lastname: Bai
authors.forename: Jan
authors.initials: J
authors.lastname: Lipfert
authors.forename: Daniel
authors.initials: D
authors.lastname: Herschlag
authors.forename: Sebastian
authors.initials: S
authors.lastname: Doniach
mesh_terms: D001667:Binding, Competitive; D002412:Cations / Q000378:metabolism; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D008956:Models, Chemical; D009690:Nucleic Acid Conformation; D009692:Nucleic Acid Heteroduplexes / Q000737:chemistry / Q000378:metabolism*; D016012:Poisson Distribution; D055672:Static Electricity
chemical_list: D002412:Cations; D009692:Nucleic Acid Heteroduplexes; D004247:DNA