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Improving the Performance of the Amber RNA Force Field by Tuning the Hydrogen-Bonding Interactions
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SYSNO ASEP 0510264 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Improving the Performance of the Amber RNA Force Field by Tuning the Hydrogen-Bonding Interactions Author(s) Kührová, P. (CZ)
Mlýnský, Vojtech (BFU-R) ORCID
Zgarbová, M. (CZ)
Krepl, Miroslav (BFU-R) ORCID
Bussi, G. (IT)
Best, R.B. (US)
Otyepka, M. (CZ)
Šponer, Jiří (BFU-R) RID, ORCID
Banáš, Pavel (BFU-R) RID, ORCIDNumber of authors 9 Source Title Journal of Chemical Theory and Computation . - : American Chemical Society - ISSN 1549-9618
Roč. 15, č. 5 (2019), s. 3288-3305Number of pages 18 s. Publication form Print - P Language eng - English Country US - United States Keywords molecular-dynamics simulations ; monovalent ion parameters ; replica-exchange ; nucleic-acids ; phosphate interactions Subject RIV CF - Physical ; Theoretical Chemistry OECD category Physical chemistry Method of publishing Limited access Institutional support BFU-R - RVO:68081707 UT WOS 000468242900045 DOI 10.1021/acs.jctc.8b00955 Annotation 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. Workplace Institute of Biophysics Contact Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244 Year of Publishing 2020 Electronic address https://pubs.acs.org/doi/10.1021/acs.jctc.8b00955
Number of the records: 1