The Kink-Turn 7 Motif: An Additional Test for RNA Force Field Performance

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F25%3A00643799" target="_blank" >RIV/68081707:_____/25:00643799 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14310/25:00142856 RIV/61989592:15640/25:73633363 RIV/61989100:27740/25:10259868

Výsledek na webu

<a href="https://pubs.acs.org/doi/10.1021/acs.jctc.5c00776" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jctc.5c00776</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jctc.5c00776" target="_blank" >10.1021/acs.jctc.5c00776</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The Kink-Turn 7 Motif: An Additional Test for RNA Force Field Performance

Popis výsledku v původním jazyce

The kink-turn is a recurrent RNA structural motif that induces a sharp bend (kink) in the A-form RNA helix. It is defined by key structural features, including consecutive sheared AG base pairs, an A-minor interaction, and multiple base-sugar interactions. An accurate representation of these densely packed noncanonical interactions by molecular dynamics simulations poses a significant challenge for contemporary force fields (FFs). Here, we present extended simulations of the ribosomal kink-turn 7 (Kt-7) from H.m., the so-called consensual kink-turn, using a broad spectrum of pair-additive and polarizable RNA FFs. None of the tested FFs manage to flawlessly describe all of the structural features of the Kt-7 although several FFs provide rather acceptable results and should not cause problems in simulations of larger RNAs containing a kink-turn. On aggregate, the widely used OL3 (ff99bsc0 chi OL3) and polarizable AMOEBA FFs achieve the best performance for this motif. Interestingly, some more recently parametrized FF variants struggle to describe the Kt-7's tertiary A-minor interaction a ubiquitous tertiary contact in RNA. This raises some concerns about the broader applicability of these FFs and suggests that they may be overfitted to small model systems, such as RNA tetranucleotides. In some cases, irreversible unkinking of the entire kink-turn motif can also be observed. The kink-turn motif is highly sensitive to variations in RNA FFs, and we strongly recommend its inclusion in training and benchmarking data sets as an important regression test to improve the robustness and accuracy of RNA FF parametrization.

Název v anglickém jazyce

The Kink-Turn 7 Motif: An Additional Test for RNA Force Field Performance

Popis výsledku anglicky

The kink-turn is a recurrent RNA structural motif that induces a sharp bend (kink) in the A-form RNA helix. It is defined by key structural features, including consecutive sheared AG base pairs, an A-minor interaction, and multiple base-sugar interactions. An accurate representation of these densely packed noncanonical interactions by molecular dynamics simulations poses a significant challenge for contemporary force fields (FFs). Here, we present extended simulations of the ribosomal kink-turn 7 (Kt-7) from H.m., the so-called consensual kink-turn, using a broad spectrum of pair-additive and polarizable RNA FFs. None of the tested FFs manage to flawlessly describe all of the structural features of the Kt-7 although several FFs provide rather acceptable results and should not cause problems in simulations of larger RNAs containing a kink-turn. On aggregate, the widely used OL3 (ff99bsc0 chi OL3) and polarizable AMOEBA FFs achieve the best performance for this motif. Interestingly, some more recently parametrized FF variants struggle to describe the Kt-7's tertiary A-minor interaction a ubiquitous tertiary contact in RNA. This raises some concerns about the broader applicability of these FFs and suggests that they may be overfitted to small model systems, such as RNA tetranucleotides. In some cases, irreversible unkinking of the entire kink-turn motif can also be observed. The kink-turn motif is highly sensitive to variations in RNA FFs, and we strongly recommend its inclusion in training and benchmarking data sets as an important regression test to improve the robustness and accuracy of RNA FF parametrization.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Journal of Chemical Theory and Computation

ISSN

1549-9618

e-ISSN

1549-9626

Svazek periodika

21

Číslo periodika v rámci svazku

24

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

14

Strana od-do

12796-12809

Kód UT WoS článku

001632716700001

EID výsledku v databázi Scopus

2-s2.0-105025360961