Fine-Tuning of the AMBER RNA Force Field with a New Term Adjusting Interactions of Terminal Nucleotides

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F20%3A00539743" target="_blank" >RIV/68081707:_____/20:00539743 - isvavai.cz</a>

Alternative codes found

RIV/61989592:15310/20:73604091

Result on the web

<a href="https://pubs.acs.org/doi/10.1021/acs.jctc.0c00228" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jctc.0c00228</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jctc.0c00228" target="_blank" >10.1021/acs.jctc.0c00228</a>

Result language

angličtina

Original language name

Fine-Tuning of the AMBER RNA Force Field with a New Term Adjusting Interactions of Terminal Nucleotides

Original language description

Determination of RNA structural-dynamic properties is challenging for experimental methods. Thus, atomistic molecular dynamics (MD) simulations represent a helpful technique complementary to experiments. However, contemporary MD methods still suffer from limitations of force fields (ffs), including imbalances in the nonbonded ff terms. We have recently demonstrated that some improvement of state-of-the-art AMBER RNA ff can be achieved by adding a new term for H-bonding called gHBfix, which increases tuning flexibility and reduces risk of side-effects. Still, the first gHBfix version did not fully correct simulations of short RNA tetranucleotides (TNs). TNs are key benchmark systems due to availability of unique NMR data, although giving too much weight on improving TN simulations can easily lead to overfitting to A-form RNA. Here we combine the gHBfix version with another term called tHBfix, which separately treats H-bond interactions formed by terminal nucleotides. This allows to refine simulations of RNA TNs without affecting simulations of other RNAs. The approach is in line with adopted strategy of current RNA Ifs, where the terminal nucleotides possess different parameters for terminal atoms than the internal nucleotides. Combination of gHBfix with tHBfix significantly improves the behavior of RNA TNs during well-converged enhanced-sampling simulations using replica exchange with solute tempering. TNs mostly populate canonical A-form like states while spurious intercalated structures are largely suppressed. Still, simulations of r(AAAA) and r(UUUU) TNs show some residual discrepancies with primary NMR data which suggests that future tuning of some other If terms might be useful. Nevertheless, the tHBfix has a clear potential to improve modeling of key biochemical processes, where interactions of RNA single stranded ends are involved.

Czech name

—

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

—

OECD FORD branch

10301 - Atomic, molecular and chemical physics (physics of atoms and molecules including collision, interaction with radiation, magnetic resonances, Mössbauer effect)

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

Publication year

2020

Confidentiality

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

Name of the periodical

Journal of Chemical Theory and Computation

ISSN

1549-9618

e-ISSN

—

Volume of the periodical

16

Issue of the periodical within the volume

6

Country of publishing house

US - UNITED STATES

Number of pages

11

Pages from-to

3936-3946

UT code for WoS article

000541503600041

EID of the result in the Scopus database

2-s2.0-85086285127