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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F17%3A00485606" target="_blank" >RIV/68081707:_____/17:00485606 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14740/17:00100461 RIV/61989592:15310/17:73584494

Výsledek na webu

<a href="http://dx.doi.org/10.1021/acs.jctc.7b00267" target="_blank" >http://dx.doi.org/10.1021/acs.jctc.7b00267</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jctc.7b00267" target="_blank" >10.1021/acs.jctc.7b00267</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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 (similar to 580 mu s 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 however, test simulations with TIP3P and OPC water models simulations were executed with the SPC/E water model, 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-mu s-scale simulations of fully folded GQs can be safely done with a number of cation,parametrization. However, there are patametrization-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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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 (similar to 580 mu s 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 however, test simulations with TIP3P and OPC water models simulations were executed with the SPC/E water model, 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-mu s-scale simulations of fully folded GQs can be safely done with a number of cation,parametrization. However, there are patametrization-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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Chemical Theory and Computation

ISSN

1549-9618

e-ISSN

—

Svazek periodika

13

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

16

Strana od-do

3911-3926

Kód UT WoS článku

000407522100040

EID výsledku v databázi Scopus

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