Can We Ever Develop an Ideal RNA Force Field? Lessons Learned from Simulations of the UUCG RNA Tetraloop and Other Systems
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F25%3A00644608" target="_blank" >RIV/68081707:_____/25:00644608 - isvavai.cz</a>
Alternative codes found
RIV/61989592:15640/25:73630702 RIV/61989100:27740/25:10257473
Result on the web
<a href="https://pubs.acs.org/doi/10.1021/acs.jctc.4c01357" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jctc.4c01357</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jctc.4c01357" target="_blank" >10.1021/acs.jctc.4c01357</a>
Alternative languages
Result language
angličtina
Original language name
Can We Ever Develop an Ideal RNA Force Field? Lessons Learned from Simulations of the UUCG RNA Tetraloop and Other Systems
Original language description
Molecular dynamics (MD) simulations are an important and well-established tool for investigating RNA structural dynamics, but their accuracy relies heavily on the quality of the employed force field (ff). In this work, we present a comprehensive evaluation of widely used pair-additive and polarizable RNA ffs using the challenging UUCG tetraloop (TL) benchmark system. Extensive standard MD simulations, initiated from the NMR structure of the 14-mer UUCG TL, revealed that most ffs did not maintain the native state, instead favoring alternative loop conformations. Notably, three very recent variants of pair-additive ffs, OL3CP-gHBfix21, DES-Amber, and OL3R2.7, successfully preserved the native structure over a 10 x 20 mu s time scale. To further assess these ffs, we performed enhanced sampling folding simulations of the shorter 8-mer UUCG TL, starting from the single-stranded conformation. Estimated folding free energies (Delta G degrees fold) varied significantly among these three ffs, with values of 0.0 +/- 0.6, 2.4 +/- 0.8, and 7.4 +/- 0.2 kcal/mol for OL3CP-gHBfix21, DES-Amber, and OL3R2.7, respectively. The Delta G degrees fold value predicted by the OL3CP-gHBfix21 ff was closest to experimental estimates, ranging from1.6 to0.7 kcal/mol. In contrast, the higher Delta G degrees fold values obtained using DES-Amber and OL3R2.7 were unexpected, suggesting that key interactions are inaccurately described in the folded, unfolded, or misfolded ensembles. These discrepancies led us to further test DES-Amber and OL3R2.7 ffs on additional RNA and DNA systems, where further performance issues were observed. Our results emphasize the complexity of accurately modeling RNA dynamics and suggest that creating an RNA ff capable of reliably performing across a wide range of RNA systems remains extremely challenging. In conclusion, our study provides valuable insights into the capabilities of current RNA ffs and highlights key areas for future ff development.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Chemical Theory and Computation
ISSN
1549-9618
e-ISSN
1549-9626
Volume of the periodical
21
Issue of the periodical within the volume
8
Country of publishing house
US - UNITED STATES
Number of pages
20
Pages from-to
4183-4202
UT code for WoS article
001396622000001
EID of the result in the Scopus database
2-s2.0-105003177523