Short-Range Imbalances in the AMBER Lennard-Jones Potential for (Deoxy)Ribose···Nucleobase Lone-Pair···pContacts in Nucleic Acids

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15640%2F21%3A73612275" target="_blank" >RIV/61989592:15640/21:73612275 - isvavai.cz</a>

Result on the web

<a href="https://pubs.acs.org/doi/10.1021/acs.jcim.1c01047" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jcim.1c01047</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jcim.1c01047" target="_blank" >10.1021/acs.jcim.1c01047</a>

Result language

angličtina

Original language name

Short-Range Imbalances in the AMBER Lennard-Jones Potential for (Deoxy)Ribose···Nucleobase Lone-Pair···pContacts in Nucleic Acids

Original language description

The lone-pair center dot center dot center dot pi (lp center dot center dot center dot pi) (deoxy)ribose center dot center dot center dot nucleobase stacking is a recurring interaction in Z-DNA and RNAs that is characterized by subvan der Waals lp center dot center dot center dot pi contacts (&lt;3.0 A). It is a part of the structural signature of CpG Z-step motifs in Z-DNA and r(UNCG) tetraloops that are known to behave poorly in molecular dynamics (MD) simulations. Although the exact origin of the MD simulation issues remains unclear, a significant part of the problem might be due to an imbalanced description of nonbonded interactions, including the characteristic lp center dot center dot center dot pi stacking. To gain insights into the links between lp center dot center dot center dot pi stacking and MD, we present an in-depth comparison between accurate large-basis-set double-hybrid Kohn-Sham density functional theory calculations DSD-BLYP-D3/ma-def2-QZVPP (DHDF-D3) and data obtained with the nonbonded potential of the AMBER force field (AFF) for NpN Z-steps (N = G, A, C, and U). Among other differences, we found that the AFF overestimates the DHDF-D3 lp center dot center dot center dot pi distances by similar to 0.1-0.2 A, while the deviation between the DHDF-D3 and AFF descriptions sharply increases in the short-range region of the interaction. Based on atom-in-molecule polarizabilities and symmetry-adapted perturbation theory analysis, we inferred that the DHDF-D3 versus AFF differences partly originate in identical nucleobase carbon atom Lennard-Jones (LJ) parameters despite the presence/absence of connected electron-withdrawing groups that lead to different effective volumes or vdW radii. Thus, to precisely model the very short CpG lp center dot center dot center dot pi contact distances, we recommend revision of the nucleobase atom LJ parameters. Additionally, we suggest that the large discrepancy between DHDF-D3 and AFF short-range repulsive part of the interaction energy potential may significantly contribute to the poor performances of MD simulations of nucleic acid systems containing Z-steps. Understanding where, and if possible why, the point-charge-type effective potentials reach their limits is vital for developing next-generation FFs and for addressing specific issues in contemporary MD simulations.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

21001 - Nano-materials (production and properties)

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

Confidentiality

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

Name of the periodical

Journal of Chemical Information and Modeling

ISSN

1549-9596

e-ISSN

—

Volume of the periodical

61

Issue of the periodical within the volume

11

Country of publishing house

US - UNITED STATES

Number of pages

14

Pages from-to

5644-5657

UT code for WoS article

000757001900031

EID of the result in the Scopus database

2-s2.0-85119611624