UUCG RNA Tetraloop as a Formidable Force-Field Challenge for MD Simulations
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F20%3A00540054" target="_blank" >RIV/68081707:_____/20:00540054 - isvavai.cz</a>
Alternative codes found
RIV/61989592:15310/20:73604594 RIV/00216224:14310/20:00117388
Result on the web
<a href="https://pubs.acs.org/doi/10.1021/acs.jctc.0c00801" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jctc.0c00801</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jctc.0c00801" target="_blank" >10.1021/acs.jctc.0c00801</a>
Alternative languages
Result language
angličtina
Original language name
UUCG RNA Tetraloop as a Formidable Force-Field Challenge for MD Simulations
Original language description
Explicit solvent atomistic molecular dynamics (MD) simulations represent an established technique to study structural dynamics of RNA molecules and an important complement for diverse experimental methods. However, performance of molecular mechanical (MM) force fields (Ifs) remains far from satisfactory even after decades of development, as apparent from a problematic structural description of some important RNA motifs. Actually, some of the smallest RNA molecules belong to the most challenging systems for MD simulations and, among them, the UUCG tetraloop is saliently difficult. We report a detailed analysis of UUCG MD ' simulations, depicting the sequence of events leading to the loss of 3finish the UUCG native state during MD simulations. The total amount of MD simulation data analyzed in this work is close to 1.3 ms. We identify molecular interactions, backbone conformations, and substates that are involved in the process. Then, we unravel specific ff deficiencies using diverse quantum mechanical/molecular mechanical (QM/MM) and QM calculations. Comparison between the MM and QM methods shows discrepancies in the description of the 5'-flanking phosphate moiety and both signature sugar-base interactions. Our work indicates that poor behavior of the UUCG tetraloop in simulations is a complex issue that cannot be attributed to one dominant and straightforwardly correctable factor. Instead, there is a concerted effect of multiple ff inaccuracies that are coupled and amplifying each other. We attempted to improve the simulation behavior by some carefully tailored interventions, but the results were still far from satisfactory, underlying the difficulties in development of accurate nucleic acid Ifs.
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
10301 - Atomic, molecular and chemical physics (physics of atoms and molecules including collision, interaction with radiation, magnetic resonances, Mössbauer effect)
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
2020
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
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Volume of the periodical
16
Issue of the periodical within the volume
12
Country of publishing house
US - UNITED STATES
Number of pages
17
Pages from-to
7601-7617
UT code for WoS article
000598208600027
EID of the result in the Scopus database
2-s2.0-85097584157