Interaction of sodium and potassium ions with sandwiched cytosine‐, guanine‐, thymine‐, and uracil‐base tetrads

Meyer, Michael; Hocquet, Alexandre; Sühnel, Jürgen

doi:10.1002/jcc.20176

Cited by 33 publications

(27 citation statements)

References 56 publications

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“…A similar conclusion referent to the structural stability of paired G‐quartets is reached in Ref. 56 with no reference to the coding aspect. Henceforth, the functional roles of quadruplex forming sequences may be reconsidered under the light of the gene and genon concepts 57…”

Section: Resultssupporting

confidence: 70%

Docking on the DNA G‐quadruplex: A molecular electrostatic potential study

2011

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The G-quadruplexes are four-stranded nucleic acid structures with guanine-rich sequences that play important biological roles in, for example, regulating telomerase association and activity. Recent evidence supports the hypothesis that the telomeric G-quadruplex DNA represents a target of novel anticancer drug medication. In this work, we present results of the molecular electrostatic potential (MEP), together with the HOMO and LUMO frontier orbitals, which are physical quantities of concern in the docking of compounds on the G-quadruplex. The calculations are performed in the frame of density functional theory at the B88LYP/6-31G* level of theory. Additional functionals that introduce dispersion effects were also taken into consideration. The MEP potential and electron density of the frontier molecular orbitals of the G-quadruplex exhibit topological deformations due to the coiled conformation of the compound when they are compared with the MEP and corresponding electron density of a DNA duplex with similar nucleic acid composition. The electrostatic active zone of the G-quadruplex is localized on the top part of the quadruplex structure where the MEP acquires the most negative values. Additional computations on a set of three daunomycins, a common anticancer drug for duplex DNA, indicate an electrostatic fastening between the quadruplex and the set of daunomycins. In this regard, the G-quadruplex electrostatic interactions favor the stacking of ligands. Finally, some implications on molecular drug design are briefly discussed.

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Section: Resultssupporting

confidence: 70%

Docking on the DNA G‐quadruplex: A molecular electrostatic potential study

2011

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“…Although far from their starting geometries, optimized tetrads in this study are in agreement with the two global minima observed in our study. In 2005, Meyer et al (16) examined such tetrads in a similar manner using density functional theory. Three optimized geometries were obtained based on model tetrads of different symmetries.…”

Section: Resultsmentioning

confidence: 99%

Guanine base stacking in G-quadruplex nucleic acids

Lech

Heddi

Phan

2012

Nucleic Acids Research

125

143

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G-quadruplexes constitute a class of nucleic acid structures defined by stacked guanine tetrads (or G-tetrads) with guanine bases from neighboring tetrads stacking with one another within the G-tetrad core. Individual G-quadruplexes can also stack with one another at their G-tetrad interface leading to higher-order structures as observed in telomeric repeat-containing DNA and RNA. In this study, we investigate how guanine base stacking influences the stability of G-quadruplexes and their stacked higher-order structures. A structural survey of the Protein Data Bank is conducted to characterize experimentally observed guanine base stacking geometries within the core of G-quadruplexes and at the interface between stacked G-quadruplex structures. We couple this survey with a systematic computational examination of stacked G-tetrad energy landscapes using quantum mechanical computations. Energy calculations of stacked G-tetrads reveal large energy differences of up to 12 kcal/mol between experimentally observed geometries at the interface of stacked G-quadruplexes. Energy landscapes are also computed using an AMBER molecular mechanics description of stacking energy and are shown to agree quite well with quantum mechanical calculated landscapes. Molecular dynamics simulations provide a structural explanation for the experimentally observed preference of parallel G-quadruplexes to stack in a 5′–5′ manner based on different accessible tetrad stacking modes at the stacking interfaces of 5′–5′ and 3′–3′ stacked G-quadruplexes.

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“…Note that while G-quartets without ions are stable in gas phase they are not stable in solution. Meyer and co-workers found that a quartet stack sandwiching the Na + with square antiprismatic coordination was by almost 10 kcal/mol more stable than a cubic coordination [101]. While the calculations likely nicely capture the correct trend the calculated energy difference is enormous, which may be due to the in vacuo environment or some other limitations (see below).…”

Section: Methodsmentioning

confidence: 96%

Molecular dynamics simulations and their application to four-stranded DNA

Šponer

Špačková

2007

Methods

128

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This review provides a critical assessment of the advantages and limitations of modeling methods available for guanine quadruplex (G-DNA) molecules. We characterize the relations of simulations to the experimental techniques and explain the actual meaning and significance of the results. The following aspects are discussed: pair-additive approximation of the empirical force fields, sampling limitations stemming from the simulation time and accuracy of description of base stacking, H-bonding, sugar-phosphate backbone and ions by force fields. Several methodological approaches complementing the classical explicit solvent molecular dynamics simulations are commented on, including enhanced sampling methods, continuum solvent methods, free energy calculations and gas phase simulations. The successes and pitfalls of recent simulation studies of G-DNA are demonstrated on selected results, including studies of cation interactions and dynamics of G-DNA stems, studies of base substitutions (inosine, thioguanine and mixed tetrads), analysis of possible kinetic intermediates in folding pathway of a G-DNA stem and analysis of loop regions of G-DNA molecules.

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Interaction of sodium and potassium ions with sandwiched cytosine‐, guanine‐, thymine‐, and uracil‐base tetrads

Cited by 33 publications

References 56 publications

Docking on the DNA G‐quadruplex: A molecular electrostatic potential study

Docking on the DNA G‐quadruplex: A molecular electrostatic potential study

Guanine base stacking in G-quadruplex nucleic acids

Molecular dynamics simulations and their application to four-stranded DNA

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