Effect of Monovalent Ion Parameters on Molecular Dynamics Simulations of G-Quadruplexes

Marek Havrila, Petr Stadlbauer, Barira Islam, Michal Otyepka, Jiří Šponer

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

G-quadruplexes (GQs) are key noncanonical DNA and RNA architectures stabilized by desolvated monovalent cations present in their central channels. We analyze extended atomistic molecular dynamics simulations (∼580 μs in total) of GQs with 11 monovalent cation parametrizations, assessing GQ overall structural stability, dynamics of internal cations, and distortions of the G-tetrad geometries. Majority of simulations were executed with the SPC/E water model; however, test simulations with TIP3P and OPC water models are also reported. The identity and parametrization of ions strongly affect behavior of a tetramolecular d[GGG]4 GQ, which is unstable with several ion parametrizations. The remaining studied RNA and DNA GQs are structurally stable, though the G-tetrad geometries are always deformed by bifurcated H-bonding in a parametrization-specific manner. Thus, basic 10-μs-scale simulations of fully folded GQs can be safely done with a number of cation parametrizations. However, there are parametrization-specific differences and basic force-field errors affecting the quantitative description of ion-tetrad interactions, which may significantly affect studies of the ion-binding processes and description of the GQ folding landscape. Our d[GGG]4 simulations indirectly suggest that such studies will also be sensitive to the water models. During exchanges with bulk water, the Na+ ions move inside the GQs in a concerted manner, while larger relocations of the K+ ions are typically separated. We suggest that the Joung-Cheatham SPC/E K+ parameters represent a safe choice in simulation studies of GQs, though variation of ion parameters can be used for specific simulation goals.

Original languageEnglish
Pages (from-to)3911-3926
Number of pages16
JournalJournal of Chemical Theory and Computation
Volume13
Issue number8
Early online date28 Jun 2017
DOIs
Publication statusPublished - 8 Aug 2017
Externally publishedYes

Fingerprint

Molecular dynamics
Ions
molecular dynamics
Computer simulation
Positive ions
ions
simulation
cations
gadolinium-gallium garnet
Monovalent Cations
Water
RNA
water
Cations
DNA
deoxyribonucleic acid
relocation
Relocation
Geometry
structural stability

Cite this

Havrila, Marek ; Stadlbauer, Petr ; Islam, Barira ; Otyepka, Michal ; Šponer, Jiří. / Effect of Monovalent Ion Parameters on Molecular Dynamics Simulations of G-Quadruplexes. In: Journal of Chemical Theory and Computation. 2017 ; Vol. 13, No. 8. pp. 3911-3926.
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Effect of Monovalent Ion Parameters on Molecular Dynamics Simulations of G-Quadruplexes. / Havrila, Marek; Stadlbauer, Petr; Islam, Barira; Otyepka, Michal; Šponer, Jiří.

In: Journal of Chemical Theory and Computation, Vol. 13, No. 8, 08.08.2017, p. 3911-3926.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effect of Monovalent Ion Parameters on Molecular Dynamics Simulations of G-Quadruplexes

AU - Havrila, Marek

AU - Stadlbauer, Petr

AU - Islam, Barira

AU - Otyepka, Michal

AU - Šponer, Jiří

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AB - G-quadruplexes (GQs) are key noncanonical DNA and RNA architectures stabilized by desolvated monovalent cations present in their central channels. We analyze extended atomistic molecular dynamics simulations (∼580 μs in total) of GQs with 11 monovalent cation parametrizations, assessing GQ overall structural stability, dynamics of internal cations, and distortions of the G-tetrad geometries. Majority of simulations were executed with the SPC/E water model; however, test simulations with TIP3P and OPC water models are also reported. The identity and parametrization of ions strongly affect behavior of a tetramolecular d[GGG]4 GQ, which is unstable with several ion parametrizations. The remaining studied RNA and DNA GQs are structurally stable, though the G-tetrad geometries are always deformed by bifurcated H-bonding in a parametrization-specific manner. Thus, basic 10-μs-scale simulations of fully folded GQs can be safely done with a number of cation parametrizations. However, there are parametrization-specific differences and basic force-field errors affecting the quantitative description of ion-tetrad interactions, which may significantly affect studies of the ion-binding processes and description of the GQ folding landscape. Our d[GGG]4 simulations indirectly suggest that such studies will also be sensitive to the water models. During exchanges with bulk water, the Na+ ions move inside the GQs in a concerted manner, while larger relocations of the K+ ions are typically separated. We suggest that the Joung-Cheatham SPC/E K+ parameters represent a safe choice in simulation studies of GQs, though variation of ion parameters can be used for specific simulation goals.

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KW - DNA/chemistry

KW - G-Quadruplexes

KW - Guanine/chemistry

KW - Molecular Dynamics Simulation

KW - Nucleic Acid Conformation

KW - Potassium/chemistry

KW - RNA/chemistry

KW - Sodium/chemistry

KW - Water/chemistry

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DO - 10.1021/acs.jctc.7b00257

M3 - Article

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SP - 3911

EP - 3926

JO - Journal of Chemical Theory and Computation

JF - Journal of Chemical Theory and Computation

SN - 1549-9618

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ER -