Multiscale Modeling of Phosphate···π Contacts in RNA U-Turns
Exposes Differences between Quantum-Chemical and AMBER Force
Field Descriptions

J 2022

Multiscale Modeling of Phosphate···π Contacts in RNA U-Turns Exposes Differences between Quantum-Chemical and AMBER Force Field Descriptions

MRÁZIKOVÁ, Klaudia, Holger KRUSE, Vojtěch MLÝNSKÝ, Pascal AUFFINGER, Jiří ŠPONER et. al.

Základní údaje

Originální název

Multiscale Modeling of Phosphate···π Contacts in RNA U-Turns Exposes Differences between Quantum-Chemical and AMBER Force Field Descriptions

Autoři

MRÁZIKOVÁ, Klaudia (703 Slovensko, domácí), Holger KRUSE, Vojtěch MLÝNSKÝ, Pascal AUFFINGER a Jiří ŠPONER (garant)

Vydání

Journal of Chemical Information and Modeling, American Chemical Society, 2022, 1549-9596

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.600

Kód RIV

RIV/00216224:14310/22:00128461

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.1021/acs.jcim.2c01064

UT WoS

000892630800001

Klíčová slova anglicky

Chemical calculations; Chemical structure; Electrostatics; Interaction energies; Nucleobases

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 31. 1. 2023 16:21, Mgr. Marie Šípková, DiS.

Anotace

V originále

Phosphate···π, also called anion···π, contacts occur between nucleobases and anionic phosphate oxygens (OP2) in r(GNRA) and r(UNNN) U-turn motifs (N = A,G,C,U; R = A,G). These contacts were investigated using state-of-the-art quantum-chemical methods (QM) to characterize their physicochemical properties and to serve as a reference to evaluate AMBER force field (AFF) performance. We found that phosphate···π interaction energies calculated with the AFF for dimethyl phosphate···nucleobase model systems are less stabilizing in comparison with double-hybrid DFT and that minimum contact distances are larger for all nucleobases. These distance stretches are also observed in large-scale AFF vs QM/MM computations and classical molecular dynamics (MD) simulations on several r(gcGNRAgc) tetraloop hairpins when compared to experimental data extracted from X-ray/cryo-EM structures (res. ≤ 2.5 Å) using the WebFR3D bioinformatic tool. MD simulations further revealed shifted OP2/nucleobase positions. We propose that discrepancies between the QM and AFF result from a combination of missing polarization in the AFF combined with too large AFF Lennard-Jones (LJ) radii of nucleobase carbon atoms in addition to an exaggerated short-range repulsion of the r–12 LJ repulsive term. We compared these results with earlier data gathered on lone pair···π contacts in CpG Z-steps occurring in r(UNCG) tetraloops. In both instances, charge transfer calculations do not support any significant n → π* donation effects. We also investigated thiophosphate···π contacts that showed reduced stabilizing interaction energies when compared to phosphate···π contacts. Thus, we challenge suggestions that the experimentally observed enhanced thermodynamic stability of phosphorothioated r(GNRA) tetraloops can be explained by larger London dispersion.

Citovat

MRÁZIKOVÁ, Klaudia, Holger KRUSE, Vojtěch MLÝNSKÝ, Pascal AUFFINGER a Jiří ŠPONER. Multiscale Modeling of Phosphate···π Contacts in RNA U-Turns Exposes Differences between Quantum-Chemical and AMBER Force Field Descriptions. Journal of Chemical Information and Modeling. American Chemical Society, 2022, roč. 62, č. 23, s. 6182-6200. ISSN 1549-9596. Dostupné z: https://dx.doi.org/10.1021/acs.jcim.2c01064.

@article{2251564,
   author = {Mráziková, Klaudia and Kruse, Holger and Mlýnský, Vojtěch and Auffinger, Pascal and Šponer, Jiří},
   article_number = {23},
   doi = {http://dx.doi.org/10.1021/acs.jcim.2c01064},
   keywords = {Chemical calculations; Chemical structure; Electrostatics; Interaction energies; Nucleobases},
   language = {eng},
   issn = {1549-9596},
   journal = {Journal of Chemical Information and Modeling},
   title = {Multiscale Modeling of Phosphate···π Contacts in RNA U-Turns Exposes Differences between Quantum-Chemical and AMBER Force Field Descriptions},
   url = {https://doi.org/10.1021/acs.jcim.2c01064},
   volume = {62},
   year = {2022}
}

TY  - JOUR
ID  - 2251564
AU  - Mráziková, Klaudia - Kruse, Holger - Mlýnský, Vojtěch - Auffinger, Pascal - Šponer, Jiří
PY  - 2022
TI  - Multiscale Modeling of Phosphate···π Contacts in RNA U-Turns Exposes Differences between Quantum-Chemical and AMBER Force Field Descriptions
JF  - Journal of Chemical Information and Modeling
VL  - 62
IS  - 23
SP  - 6182-6200
EP  - 6182-6200
PB  - American Chemical Society
SN  - 15499596
KW  - Chemical calculations
KW  - Chemical structure
KW  - Electrostatics
KW  - Interaction energies
KW  - Nucleobases
UR  - https://doi.org/10.1021/acs.jcim.2c01064
N2  - Phosphate···π, also called anion···π, contacts occur between nucleobases and anionic phosphate oxygens (OP2) in r(GNRA) and r(UNNN) U-turn motifs (N = A,G,C,U; R = A,G). These contacts were investigated using state-of-the-art quantum-chemical methods (QM) to characterize their physicochemical properties and to serve as a reference to evaluate AMBER force field (AFF) performance. We found that phosphate···π interaction energies calculated with the AFF for dimethyl phosphate···nucleobase model systems are less stabilizing in comparison with double-hybrid DFT and that minimum contact distances are larger for all nucleobases. These distance stretches are also observed in large-scale AFF vs QM/MM computations and classical molecular dynamics (MD) simulations on several r(gcGNRAgc) tetraloop hairpins when compared to experimental data extracted from X-ray/cryo-EM structures (res. ≤ 2.5 Å) using the WebFR3D bioinformatic tool. MD simulations further revealed shifted OP2/nucleobase positions. We propose that discrepancies between the QM and AFF result from a combination of missing polarization in the AFF combined with too large AFF Lennard-Jones (LJ) radii of nucleobase carbon atoms in addition to an exaggerated short-range repulsion of the r–12 LJ repulsive term. We compared these results with earlier data gathered on lone pair···π contacts in CpG Z-steps occurring in r(UNCG) tetraloops. In both instances, charge transfer calculations do not support any significant n → π* donation effects. We also investigated thiophosphate···π contacts that showed reduced stabilizing interaction energies when compared to phosphate···π contacts. Thus, we challenge suggestions that the experimentally observed enhanced thermodynamic stability of phosphorothioated r(GNRA) tetraloops can be explained by larger London dispersion.
ER  -

MRÁZIKOVÁ, Klaudia, Holger KRUSE, Vojtěch MLÝNSKÝ, Pascal AUFFINGER a Jiří ŠPONER. Multiscale Modeling of Phosphate···π Contacts in RNA U-Turns Exposes Differences between Quantum-Chemical and AMBER Force Field Descriptions. \textit{Journal of Chemical Information and Modeling}. American Chemical Society, 2022, roč.~62, č.~23, s.~6182-6200. ISSN~1549-9596. Dostupné z: https://dx.doi.org/10.1021/acs.jcim.2c01064.

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