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Simple Adjustment of Intranucleotide Base-Phosphate Interaction in the OL3 AMBER Force Field Improves RNA Simulations
[Image: see text] Molecular dynamics (MD) simulations represent an established tool to study RNA molecules. The outcome of MD studies depends, however, on the quality of the force field (ff). Here we suggest a correction for the widely used AMBER OL3 ff by adding a simple adjustment of the nonbonded...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687871/ https://www.ncbi.nlm.nih.gov/pubmed/37944118 http://dx.doi.org/10.1021/acs.jctc.3c00990 |
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author | Mlýnský, Vojtěch Kührová, Petra Stadlbauer, Petr Krepl, Miroslav Otyepka, Michal Banáš, Pavel Šponer, Jiří |
author_facet | Mlýnský, Vojtěch Kührová, Petra Stadlbauer, Petr Krepl, Miroslav Otyepka, Michal Banáš, Pavel Šponer, Jiří |
author_sort | Mlýnský, Vojtěch |
collection | PubMed |
description | [Image: see text] Molecular dynamics (MD) simulations represent an established tool to study RNA molecules. The outcome of MD studies depends, however, on the quality of the force field (ff). Here we suggest a correction for the widely used AMBER OL3 ff by adding a simple adjustment of the nonbonded parameters. The reparameterization of the Lennard–Jones potential for the −H8···O5′– and −H6···O5′– atom pairs addresses an intranucleotide steric clash occurring in the type 0 base-phosphate interaction (0BPh). The nonbonded fix (NBfix) modification of 0BPh interactions (NBfix(0BPh) modification) was tuned via a reweighting approach and subsequently tested using an extensive set of standard and enhanced sampling simulations of both unstructured and folded RNA motifs. The modification corrects minor but visible intranucleotide clash for the anti nucleobase conformation. We observed that structural ensembles of small RNA benchmark motifs simulated with the NBfix(0BPh) modification provide better agreement with experiments. No side effects of the modification were observed in standard simulations of larger structured RNA motifs. We suggest that the combination of OL3 RNA ff and NBfix(0BPh) modification is a viable option to improve RNA MD simulations. |
format | Online Article Text |
id | pubmed-10687871 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-106878712023-12-01 Simple Adjustment of Intranucleotide Base-Phosphate Interaction in the OL3 AMBER Force Field Improves RNA Simulations Mlýnský, Vojtěch Kührová, Petra Stadlbauer, Petr Krepl, Miroslav Otyepka, Michal Banáš, Pavel Šponer, Jiří J Chem Theory Comput [Image: see text] Molecular dynamics (MD) simulations represent an established tool to study RNA molecules. The outcome of MD studies depends, however, on the quality of the force field (ff). Here we suggest a correction for the widely used AMBER OL3 ff by adding a simple adjustment of the nonbonded parameters. The reparameterization of the Lennard–Jones potential for the −H8···O5′– and −H6···O5′– atom pairs addresses an intranucleotide steric clash occurring in the type 0 base-phosphate interaction (0BPh). The nonbonded fix (NBfix) modification of 0BPh interactions (NBfix(0BPh) modification) was tuned via a reweighting approach and subsequently tested using an extensive set of standard and enhanced sampling simulations of both unstructured and folded RNA motifs. The modification corrects minor but visible intranucleotide clash for the anti nucleobase conformation. We observed that structural ensembles of small RNA benchmark motifs simulated with the NBfix(0BPh) modification provide better agreement with experiments. No side effects of the modification were observed in standard simulations of larger structured RNA motifs. We suggest that the combination of OL3 RNA ff and NBfix(0BPh) modification is a viable option to improve RNA MD simulations. American Chemical Society 2023-11-09 /pmc/articles/PMC10687871/ /pubmed/37944118 http://dx.doi.org/10.1021/acs.jctc.3c00990 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Mlýnský, Vojtěch Kührová, Petra Stadlbauer, Petr Krepl, Miroslav Otyepka, Michal Banáš, Pavel Šponer, Jiří Simple Adjustment of Intranucleotide Base-Phosphate Interaction in the OL3 AMBER Force Field Improves RNA Simulations |
title | Simple Adjustment
of Intranucleotide Base-Phosphate
Interaction in the OL3 AMBER Force Field Improves RNA Simulations |
title_full | Simple Adjustment
of Intranucleotide Base-Phosphate
Interaction in the OL3 AMBER Force Field Improves RNA Simulations |
title_fullStr | Simple Adjustment
of Intranucleotide Base-Phosphate
Interaction in the OL3 AMBER Force Field Improves RNA Simulations |
title_full_unstemmed | Simple Adjustment
of Intranucleotide Base-Phosphate
Interaction in the OL3 AMBER Force Field Improves RNA Simulations |
title_short | Simple Adjustment
of Intranucleotide Base-Phosphate
Interaction in the OL3 AMBER Force Field Improves RNA Simulations |
title_sort | simple adjustment
of intranucleotide base-phosphate
interaction in the ol3 amber force field improves rna simulations |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687871/ https://www.ncbi.nlm.nih.gov/pubmed/37944118 http://dx.doi.org/10.1021/acs.jctc.3c00990 |
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