Improving the Performance of the Amber RNA Force Field by Tuning the Hydrogen-Bonding Interactions

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F19%3A00510264" target="_blank" >RIV/68081707:_____/19:00510264 - isvavai.cz</a>

Alternative codes found

RIV/61989592:15310/19:73597722

Result on the web

<a href="https://pubs.acs.org/doi/10.1021/acs.jctc.8b00955" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jctc.8b00955</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jctc.8b00955" target="_blank" >10.1021/acs.jctc.8b00955</a>

Result language

angličtina

Original language name

Improving the Performance of the Amber RNA Force Field by Tuning the Hydrogen-Bonding Interactions

Original language description

Molecular dynamics (MD) simulations became a leading tool for investigation of structural dynamics of nucleic acids. Despite recent efforts to improve the empirical potentials (force fields, ffs), RNA ifs have persisting deficiencies, which hamper their utilization in quantitatively accurate simulations. Previous studies have shown that at least two salient problems contribute to difficulties in the description of free-energy landscapes of small RNA motifs: (i) excessive stabilization of the unfolded single-stranded RNA ensemble by intramolecular base-phosphate and sugar-phosphate interactions and (ii) destabilization of the native folded state by underestimation of stability of base pairing. Here, we introduce a general ff term (gHBfix) that can selectively fine-tune nonbonding interaction terms in RNA ifs, in particular, the H bonds. The gHBfix potential affects the pairwise interactions between all possible pairs of the specific atom types, while all other interactions remain intact, i.e., it is not a structure-based model. In order to probe the ability of the gHBfix potential to refine the ff nonbonded terms, we performed an extensive set of folding simulations of RNA tetranucleotides and tetraloops. On the basis of these data, we propose particular gHBfix parameters to modify the AMBER RNA ff. The suggested parametrization significantly improves the agreement between experimental data and the simulation conformational ensembles, although our current ff version still remains far from being flawless. While attempts to tune the RNA ffs by conventional reparametrizations of dihedral potentials or nonbonded terms can lead to major undesired side effects, as we demonstrate for some recently published ffs, gHBfix has a clear promising potential to improve the If performance while avoiding introduction of major new imbalances.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10403 - Physical 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

2019

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

15

Issue of the periodical within the volume

5

Country of publishing house

US - UNITED STATES

Number of pages

18

Pages from-to

3288-3305

UT code for WoS article

000468242900045

EID of the result in the Scopus database

—