Toward Convergence in Folding Simulations of RNA Tetraloops : Comparison of Enhanced Sampling Techniques and Effects of Force Field Modifications br

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F22%3A00557417" target="_blank" >RIV/68081707:_____/22:00557417 - isvavai.cz</a>

Result on the web

<a href="https://pubs.acs.org/doi/10.1021/acs.jctc.1c01222" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jctc.1c01222</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jctc.1c01222" target="_blank" >10.1021/acs.jctc.1c01222</a>

Result language

angličtina

Original language name

Toward Convergence in Folding Simulations of RNA Tetraloops : Comparison of Enhanced Sampling Techniques and Effects of Force Field Modifications br

Original language description

Atomistic molecular dynamics simulations repre-sent an established technique for investigation of RNA structuraldynamics. Despite continuous development, contemporary RNAsimulations still suffer from suboptimal accuracy of empiricalpotentials (forcefields,ffs) and sampling limitations. Developmentof efficient enhanced sampling techniques is important for tworeasons. First, they allow us to overcome the sampling limitations,and second, they can be used to quantifyffimbalances providedthey reach a sufficient convergence. Here, we study two RNAtetraloops (TLs), namely the GAGA and UUCG motifs. Weperform extensive folding simulations and calculate folding freeenergies (Delta Gfold degrees) with the aim to compare different enhancedsampling techniques and to test several modifications of thenonbonded terms extending the AMBER OL3 RNAff. We demonstrate that replica-exchange solute tempering (REST2)simulations with 12-16 replicas do not show any sign of convergence even when extended to a timescale of 120 mu s per replica.However, the combination of REST2 with well-tempered metadynamics (ST-MetaD) achieves good convergence on a timescale of5-10 mu s per replica, improving the sampling efficiency by at least 2 orders of magnitude. Effects offfmodifications on Delta Gfold degrees energies were initially explored by the reweighting approach and then validated by new simulations. We tested several manuallyprepared variants of the gHBfix potential which improve stability of the native state of both TLs by similar to 2 kcal/mol. This is sufficient toconveniently stabilize the folded GAGA TL while the UUCG TL still remains under-stabilized. Appropriate adjustment of van derWaals parameters for C-HmiddotmiddotmiddotO5 ' base-phosphate interaction may further stabilize the native states of both TLs by similar to 0.6 kcal/mol

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

10401 - Organic chemistry

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

2022

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

1549-9626

Volume of the periodical

18

Issue of the periodical within the volume

4

Country of publishing house

US - UNITED STATES

Number of pages

15

Pages from-to

2642-2656

UT code for WoS article

000789656500048

EID of the result in the Scopus database

2-s2.0-85128215230