Noncanonical alpha/gamma Backbone Conformations in RNA and the Accuracy of Their Description by the AMBER Force Field

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F17%3A73584325" target="_blank" >RIV/61989592:15310/17:73584325 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68081707:_____/17:00476549

Výsledek na webu

<a href="http://pubs.acs.org/doi/pdf/10.1021/acs.jpcb.7b00262" target="_blank" >http://pubs.acs.org/doi/pdf/10.1021/acs.jpcb.7b00262</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jpcb.7b00262" target="_blank" >10.1021/acs.jpcb.7b00262</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Noncanonical alpha/gamma Backbone Conformations in RNA and the Accuracy of Their Description by the AMBER Force Field

Popis výsledku v původním jazyce

The sugar-phosphate backbone of RNA can exist in diverse rotameric substates, giving RNA molecules enormous conformational variability. The most frequent noncanonical backbone conformation in RNA is alpha/gamma = t/t, which is derived from the canonical backbone by a crankshaft motion and largely preserves the standard geometry of the RNA duplex. A similar conformation also exists in DNA, where it has been extensively studied and shown to be involved in DNA-protein interactions. However, the function of the alpha/gamma = t/t conformation in RNA is poorly understood. Here, we present molecular dynamics simulations of several prototypical RNA structures obtained from X-ray and NMR experiments, including canonical and mismatched RNA duplexes, UUCG and GAGA tetraloops, Loop E, the sarcin ricin loop, a parallel guanine quadruplex, and a viral pseudoknot. The stability of various noncanonical alpha/gamma backbone conformations was analyzed with two AMBER force fields, ff99bscO chi(OL3) and ff99bscO chi(OL3) with the recent epsilon zeta(OL1) and beta(OL1) corrections for DNA. Although some alpha/gamma substates were stable with seemingly well-described equilibria, many were unstable in our simulations. Notably, the most frequent noncanonical conformer alpha/gamma = t/t was unstable in both tested force fields. Possible reasons for this instability are discussed. Our work reveals a potentially important artifact in RNA force fields and highlights a need for further force field refinement.

Název v anglickém jazyce

Noncanonical alpha/gamma Backbone Conformations in RNA and the Accuracy of Their Description by the AMBER Force Field

Popis výsledku anglicky

The sugar-phosphate backbone of RNA can exist in diverse rotameric substates, giving RNA molecules enormous conformational variability. The most frequent noncanonical backbone conformation in RNA is alpha/gamma = t/t, which is derived from the canonical backbone by a crankshaft motion and largely preserves the standard geometry of the RNA duplex. A similar conformation also exists in DNA, where it has been extensively studied and shown to be involved in DNA-protein interactions. However, the function of the alpha/gamma = t/t conformation in RNA is poorly understood. Here, we present molecular dynamics simulations of several prototypical RNA structures obtained from X-ray and NMR experiments, including canonical and mismatched RNA duplexes, UUCG and GAGA tetraloops, Loop E, the sarcin ricin loop, a parallel guanine quadruplex, and a viral pseudoknot. The stability of various noncanonical alpha/gamma backbone conformations was analyzed with two AMBER force fields, ff99bscO chi(OL3) and ff99bscO chi(OL3) with the recent epsilon zeta(OL1) and beta(OL1) corrections for DNA. Although some alpha/gamma substates were stable with seemingly well-described equilibria, many were unstable in our simulations. Notably, the most frequent noncanonical conformer alpha/gamma = t/t was unstable in both tested force fields. Possible reasons for this instability are discussed. Our work reveals a potentially important artifact in RNA force fields and highlights a need for further force field refinement.

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 Physical Chemistry B

ISSN

1520-6106

e-ISSN

—

Svazek periodika

121

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

14

Strana od-do

2420-2433

Kód UT WoS článku

000397546200005

EID výsledku v databázi Scopus

2-s2.0-85019699402