Stability of Two-Quartet G-Quadruplexes and Their Dimers in Atomistic Simulations

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F20%3A00536138" target="_blank" >RIV/68081707:_____/20:00536138 - isvavai.cz</a>

Alternative codes found

RIV/61989592:15310/20:73604090

Result on the web

<a href="https://pubs.acs.org/doi/10.1021/acs.jctc.9b01068" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jctc.9b01068</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jctc.9b01068" target="_blank" >10.1021/acs.jctc.9b01068</a>

Result language

angličtina

Original language name

Stability of Two-Quartet G-Quadruplexes and Their Dimers in Atomistic Simulations

Original language description

G-quadruplexes (GQs) are four-stranded noncanonical DNA and RNA architectures that can be formed by guanine-rich sequences. The stability of GQs increases with the number of G-quartets, and three G-quartets generally form stable GQs. However, the stability of two-quartet GQs is an open issue. To understand the intrinsic stability of two-quartet GQ stems, we have carried out a series of unbiased molecular dynamics (MD) simulations (505 mu s in total) of two- and four-quartet DNA and RNA GQs, with attention paid mainly to parallel-stranded arrangements. We used AMBER DNA parmOL15 and RNA parmOL3 force fields and tested different ion and water models. Two-quartet parallel-stranded DNA GQs unfolded in all the simulations, while the equivalent RNA GQ was stable in most of the simulations. GQs composed of two stacked units of two-quartet GQs were stable for both DNA and RNA. The simulations suggest that a minimum of three quartets are needed to form an intrinsically stable all-anti parallel-stranded DNA GQ Parallel two-quartet DNA GQ may exist if substantially stabilized by another molecule or structural element, including multimerization. On the other hand, we predict that isolated RNA two-quartet parallel GQs may form, albeit being weakly stable. We also show that ionic parameters and water models should be chosen with caution because some parameter combinations can cause spurious instability of GQ stems. Some in-so-far unnoticed limitations of force-field description of multiple ions inside the GQs are discussed, which compromise the capability of simulations to fully capture the effect of increase in the number of quartets on the GQ stability.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10403 - Physical chemistry

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

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

Name of the periodical

Journal of Chemical Theory and Computation

ISSN

1549-9618

e-ISSN

—

Volume of the periodical

16

Issue of the periodical within the volume

6

Country of publishing house

US - UNITED STATES

Number of pages

17

Pages from-to

3447-3463

UT code for WoS article

000541503600001

EID of the result in the Scopus database

2-s2.0-85086282140