Proton transfer in guanine-cytosine base pair analogues studied by NMR spectroscopy and PIMD simulations

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F18%3A00499337" target="_blank" >RIV/61388963:_____/18:00499337 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60461373:22340/18:43916704

Výsledek na webu

<a href="https://pubs.rsc.org/en/content/articlehtml/2018/fd/c8fd00070k" target="_blank" >https://pubs.rsc.org/en/content/articlehtml/2018/fd/c8fd00070k</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/c8fd00070k" target="_blank" >10.1039/c8fd00070k</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Proton transfer in guanine-cytosine base pair analogues studied by NMR spectroscopy and PIMD simulations

Popis výsledku v původním jazyce

It has been hypothesised that proton tunnelling between paired nucleobases significantly enhances the formation of rare tautomeric forms and hence leads to errors in DNA replication. Here, we study nuclear quantum effects (NQEs) using deuterium isotope-induced changes of nitrogen NMR chemical shifts in a model base pair consisting of two tautomers of isocytosine, which form hydrogen-bonded dimers in the same way as the guanine-cytosine base pair. Isotope effects in NMR are consequences of NQEs, because ro-vibrational averaging of different isotopologues gives rise to different magnetic shielding of the nuclei. The experimental deuterium-induced chemical shift changes are compared with those calculated by a combination of path integral molecular dynamics (PIMD) simulations with DFT calculations of nuclear shielding. These calculations can directly link the observable isotope-induced shifts with NQEs. A comparison of the deuterium-induced changes of N-15 chemical shifts with those predicted by PIMD simulations shows that inter-base proton transfer reactions do not take place in this system. We demonstrate, however, that NMR isotope shifts provide a unique possibility to study NQEs and to evaluate the accuracy of the computational methods used for modelling quantum effects in molecules. Calculations based on the PBE functional from the general-gradient-approximation family provided significantly worse predictions of deuterium isotope shifts than those with the hybrid B3LYP functional.

Název v anglickém jazyce

Proton transfer in guanine-cytosine base pair analogues studied by NMR spectroscopy and PIMD simulations

Popis výsledku anglicky

It has been hypothesised that proton tunnelling between paired nucleobases significantly enhances the formation of rare tautomeric forms and hence leads to errors in DNA replication. Here, we study nuclear quantum effects (NQEs) using deuterium isotope-induced changes of nitrogen NMR chemical shifts in a model base pair consisting of two tautomers of isocytosine, which form hydrogen-bonded dimers in the same way as the guanine-cytosine base pair. Isotope effects in NMR are consequences of NQEs, because ro-vibrational averaging of different isotopologues gives rise to different magnetic shielding of the nuclei. The experimental deuterium-induced chemical shift changes are compared with those calculated by a combination of path integral molecular dynamics (PIMD) simulations with DFT calculations of nuclear shielding. These calculations can directly link the observable isotope-induced shifts with NQEs. A comparison of the deuterium-induced changes of N-15 chemical shifts with those predicted by PIMD simulations shows that inter-base proton transfer reactions do not take place in this system. We demonstrate, however, that NMR isotope shifts provide a unique possibility to study NQEs and to evaluate the accuracy of the computational methods used for modelling quantum effects in molecules. Calculations based on the PBE functional from the general-gradient-approximation family provided significantly worse predictions of deuterium isotope shifts than those with the hybrid B3LYP functional.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

<a href="/cs/project/GA18-11851S" target="_blank" >GA18-11851S: Intermolekulární interakce studované pomocí NMR spektroskopie a pokročilých kvantově chemických výpočtů</a><br>

Návaznosti

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

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Faraday Discussions

ISSN

1359-6640

e-ISSN

—

Svazek periodika

212

Číslo periodika v rámci svazku

Dec 1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

14

Strana od-do

331-344

Kód UT WoS článku

000455021000016

EID výsledku v databázi Scopus

2-s2.0-85054544876