Comparative Assessment of Different RNA Tetranucleotides from the DFT-D3 and Force Field Perspective

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F16%3A00471951" target="_blank" >RIV/68081707:_____/16:00471951 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14740/16:00088714

Výsledek na webu

<a href="http://dx.doi.org/10.1021/acs.jpcb.6b07551" target="_blank" >http://dx.doi.org/10.1021/acs.jpcb.6b07551</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jpcb.6b07551" target="_blank" >10.1021/acs.jpcb.6b07551</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Comparative Assessment of Different RNA Tetranucleotides from the DFT-D3 and Force Field Perspective

Popis výsledku v původním jazyce

Classical force field (FF) molecular dynamics (MD) simulations of RNA tetranucleotides have substantial problems in reproducing conformer populations indicated by NMR experiments. To provide more information about the possible sources of errors, we performed quantum mechanical (QM, TPSS-D3/def2-TZVP) and molecular mechanics (MM, AMBER parm99bsc0+X-OL3) calculations of different r(CCCC), r(GACC), and r(UUUU) conformers obtained from explicit solvent MD simulations. Solvent effects in the static QM and MM calculations were mimicked using implicit solvent models (COSMO and Poisson-Boltzmann, respectively). The comparison of QM and MM geometries and energies revealed that the two methodologies provide qualitatively consistent results in most of the cases. Even though we found some differences, these were insufficient to indicate any systematic corrections of the RNA FF terms that could improve the performance of classical MD in simulating tetranucleotides. On the basis of these findings, we inferred that the overpopulation of intercalated conformers in the MD simulations of RNA tetramers, which were not observed experimentally, might be predominantly caused by imbalanced water-solvent and water-water interactions. Apart from the large-scale QM calculations performed to assess the performance of the AMBER FF, a representative spectrum of faster QM methods was tested.

Název v anglickém jazyce

Comparative Assessment of Different RNA Tetranucleotides from the DFT-D3 and Force Field Perspective

Popis výsledku anglicky

Classical force field (FF) molecular dynamics (MD) simulations of RNA tetranucleotides have substantial problems in reproducing conformer populations indicated by NMR experiments. To provide more information about the possible sources of errors, we performed quantum mechanical (QM, TPSS-D3/def2-TZVP) and molecular mechanics (MM, AMBER parm99bsc0+X-OL3) calculations of different r(CCCC), r(GACC), and r(UUUU) conformers obtained from explicit solvent MD simulations. Solvent effects in the static QM and MM calculations were mimicked using implicit solvent models (COSMO and Poisson-Boltzmann, respectively). The comparison of QM and MM geometries and energies revealed that the two methodologies provide qualitatively consistent results in most of the cases. Even though we found some differences, these were insufficient to indicate any systematic corrections of the RNA FF terms that could improve the performance of classical MD in simulating tetranucleotides. On the basis of these findings, we inferred that the overpopulation of intercalated conformers in the MD simulations of RNA tetramers, which were not observed experimentally, might be predominantly caused by imbalanced water-solvent and water-water interactions. Apart from the large-scale QM calculations performed to assess the performance of the AMBER FF, a representative spectrum of faster QM methods was tested.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

BO - Biofyzika

OECD FORD obor

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Projekt

<a href="/cs/project/GBP305%2F12%2FG034" target="_blank" >GBP305/12/G034: Centrum biologie RNA</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

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

120

Číslo periodika v rámci svazku

41

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

14

Strana od-do

10635-10648

Kód UT WoS článku

000386107500003

EID výsledku v databázi Scopus

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