title: Channeling through Two Stacked Guanine Quartets of One and Two Alkali Cations in the Li+, Na+, K+, and Rb+Series. Assessment of the Accuracy of the SIBFA Anisotropic Polarizable Molecular Mechanics Potential.
abstract: Stacking of guanine quartets (GQs) can trigger the formation of DNA or RNA quadruple helices, which play numerous biochemical roles. The GQs are stabilized by alkali cations, mainly K+and Na+, which can reside in, or channel through, the central axis of the GQ stems. Further, ion conduction through GQ wires can be leveraged for nanochemistry applications. G-quadruplex systems have been extensively studied by classical molecular dynamics (MD) simulations using pair-additive force fields or by quantum-chemical (QC) calculations. However, the non-polarizable force fields are very approximate, while QC calculations lack the necessary sampling. Thus, ultimate description of GQ systems would require long-enough simulations using advanced polarizable molecular mechanics (MM). However, to perform such calculations, it is first mandatory to evaluate the method's accuracy using benchmark QC. We report such an evaluation for SIBFA polarizable MM, bearing on the channeling (movement) of an alkali cation (Li+, Na+, K+, or Rb+) along the axis of two stacked G quartets interacting with either one or two ions. The QC energy profiles display markedly different features depending upon the cation but can be retrieved in the majority of cases by the SIBFA profiles. An appropriate balance of first-order (electrostatic and short-range repulsion) and second-order (polarization, charge-transfer, and dispersion) contributions within ΔE is mandatory. With two cations in the channel, the relative weights of the second-order contributions increase steadily upon increasing the ion size. In the G8 complexes with two K+or two Rb+cations, the sum of polarization and charge-transfer exceeds the first order terms for all ion positions.
authors.affiliation: Laboratoire de Chimie Théorique, Sorbonne Universités , UPMC, UMR7616 CNRS, 75006Paris, France.
authors.forename: Nohad
authors.identifier: 0000-0001-7174-2907
authors.initials: N
authors.lastname: Gresh
authors.affiliation: Laboratoire de Chimie Théorique, Sorbonne Universités , UPMC, UMR7616 CNRS, 75006Paris, France.
authors.forename: Sehr
authors.initials: S
authors.lastname: Naseem-Khan
authors.affiliation: Laboratoire de Chimie Théorique, Sorbonne Universités , UPMC, UMR7616 CNRS, 75006Paris, France.
authors.forename: Louis
authors.initials: L
authors.lastname: Lagardère
authors.affiliation: Laboratoire de Chimie Théorique, Sorbonne Universités , UPMC, UMR7616 CNRS, 75006Paris, France.|Institut Universitaire de France, Paris Cedex 05, 75231, France.|Department of Biomedical Engineering, The University of Texas at Austin , Austin, Texas, 78712, United States.
authors.forename: Jean-Philip
authors.identifier: 0000-0001-6615-9426
authors.initials: JP
authors.lastname: Piquemal
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic , Kralovpolska 135, 612 65 Brno, Czech Republic.|CEITEC - Central European Institute of Technology, Masaryk University , Campus Bohunice, Kamenice 5, 625 00 Brno, Czech Republic.
authors.forename: Judit E
authors.initials: JE
authors.lastname: Sponer
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic , Kralovpolska 135, 612 65 Brno, Czech Republic.|CEITEC - Central European Institute of Technology, Masaryk University , Campus Bohunice, Kamenice 5, 625 00 Brno, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Sponer
mesh_terms: D000468:Alkalies / Q000737:chemistry; D016880:Anisotropy; D002414:Cations, Monovalent / Q000737:chemistry; D054856:G-Quadruplexes; D006147:Guanine / Q000737:chemistry*; D008094:Lithium / Q000737:chemistry*; D008958:Models, Molecular; D011188:Potassium / Q000737:chemistry*; D012413:Rubidium / Q000737:chemistry*; D012964:Sodium / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D000468:Alkalies; D002414:Cations, Monovalent; D006147:Guanine; D008094:Lithium; D012964:Sodium; D012413:Rubidium; D011188:Potassium