Exploring the Dynamics of Propeller Loops in Human Telomeric DNA Quadruplexes Using Atomistic Simulations

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F17%3A00485734" target="_blank" >RIV/68081707:_____/17:00485734 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/17:73584502

Výsledek na webu

<a href="http://dx.doi.org/10.1021/acs.jctc.7b00226" target="_blank" >http://dx.doi.org/10.1021/acs.jctc.7b00226</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jctc.7b00226" target="_blank" >10.1021/acs.jctc.7b00226</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Exploring the Dynamics of Propeller Loops in Human Telomeric DNA Quadruplexes Using Atomistic Simulations

Popis výsledku v původním jazyce

We have carried out a series of extended unbiased molecular dynamics (MD) simulations (up to 10 its long, similar to 162 mu s in total) complemented by replica-exchange with the collective variable tempering (RECT) approach for several human telomeric DNA G-quadruplex (GQ) topologies with TTA propeller loops. We used different AMBER DNA force-field variants and also processed simulations by Markov State Model (MSM) analysis. The slow conformational transitions in the propeller loops took place on a scale of a few,us, emphasizing the need for long simulations in studies of GQ dynamics. The propeller loops sampled similar ensembles for all GQtopologies and for all force field dihedral-potential variants. The outcomes of standard and RECT simulations were consistent and captured similar spectrum of loop conformations. However, the most common crystallographic loop conformation was very unstable with all force-field versions. Although the loss of canonical gamma-trans state of the first propeller loop nucleotide could be related to the indispensable bsc0 alpha/gamma dihedral potential, even supporting this particular dihedral by a bias was insufficient to populate the experimentally dominant loop conformation. In conclusion, while our simulations were capable of providing a reasonable albeit not converged sampling of the TTA propeller loop conformational space, the force-field description still remained far from satisfactory.

Název v anglickém jazyce

Exploring the Dynamics of Propeller Loops in Human Telomeric DNA Quadruplexes Using Atomistic Simulations

Popis výsledku anglicky

We have carried out a series of extended unbiased molecular dynamics (MD) simulations (up to 10 its long, similar to 162 mu s in total) complemented by replica-exchange with the collective variable tempering (RECT) approach for several human telomeric DNA G-quadruplex (GQ) topologies with TTA propeller loops. We used different AMBER DNA force-field variants and also processed simulations by Markov State Model (MSM) analysis. The slow conformational transitions in the propeller loops took place on a scale of a few,us, emphasizing the need for long simulations in studies of GQ dynamics. The propeller loops sampled similar ensembles for all GQtopologies and for all force field dihedral-potential variants. The outcomes of standard and RECT simulations were consistent and captured similar spectrum of loop conformations. However, the most common crystallographic loop conformation was very unstable with all force-field versions. Although the loss of canonical gamma-trans state of the first propeller loop nucleotide could be related to the indispensable bsc0 alpha/gamma dihedral potential, even supporting this particular dihedral by a bias was insufficient to populate the experimentally dominant loop conformation. In conclusion, while our simulations were capable of providing a reasonable albeit not converged sampling of the TTA propeller loop conformational space, the force-field description still remained far from satisfactory.

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

6

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

23

Strana od-do

2458-2480

Kód UT WoS článku

000403530100010

EID výsledku v databázi Scopus

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