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Empirical Corrections to the Amber RNA Force Field with Target Metadynamics

[Image: see text] The computational study of conformational transitions in nucleic acids still faces many challenges. For example, in the case of single stranded RNA tetranucleotides, agreement between simulations and experiments is not satisfactory due to inaccuracies in the force fields commonly u...

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Autores principales: Gil-Ley, Alejandro, Bottaro, Sandro, Bussi, Giovanni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2016
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910146/
https://www.ncbi.nlm.nih.gov/pubmed/27153317
http://dx.doi.org/10.1021/acs.jctc.6b00299
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author Gil-Ley, Alejandro
Bottaro, Sandro
Bussi, Giovanni
author_facet Gil-Ley, Alejandro
Bottaro, Sandro
Bussi, Giovanni
author_sort Gil-Ley, Alejandro
collection PubMed
description [Image: see text] The computational study of conformational transitions in nucleic acids still faces many challenges. For example, in the case of single stranded RNA tetranucleotides, agreement between simulations and experiments is not satisfactory due to inaccuracies in the force fields commonly used in molecular dynamics simulations. We here use experimental data collected from high-resolution X-ray structures to attempt an improvement of the latest version of the AMBER force field. A modified metadynamics algorithm is used to calculate correcting potentials designed to enforce experimental distributions of backbone torsion angles. Replica-exchange simulations of tetranucleotides including these correcting potentials show significantly better agreement with independent solution experiments for the oligonucleotides containing pyrimidine bases. Although the proposed corrections do not seem to be portable to generic RNA systems, the simulations revealed the importance of the α and ζ backbone angles for the modulation of the RNA conformational ensemble. The correction protocol presented here suggests a systematic procedure for force-field refinement.
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spelling pubmed-49101462016-06-20 Empirical Corrections to the Amber RNA Force Field with Target Metadynamics Gil-Ley, Alejandro Bottaro, Sandro Bussi, Giovanni J Chem Theory Comput [Image: see text] The computational study of conformational transitions in nucleic acids still faces many challenges. For example, in the case of single stranded RNA tetranucleotides, agreement between simulations and experiments is not satisfactory due to inaccuracies in the force fields commonly used in molecular dynamics simulations. We here use experimental data collected from high-resolution X-ray structures to attempt an improvement of the latest version of the AMBER force field. A modified metadynamics algorithm is used to calculate correcting potentials designed to enforce experimental distributions of backbone torsion angles. Replica-exchange simulations of tetranucleotides including these correcting potentials show significantly better agreement with independent solution experiments for the oligonucleotides containing pyrimidine bases. Although the proposed corrections do not seem to be portable to generic RNA systems, the simulations revealed the importance of the α and ζ backbone angles for the modulation of the RNA conformational ensemble. The correction protocol presented here suggests a systematic procedure for force-field refinement. American Chemical Society 2016-05-06 2016-06-14 /pmc/articles/PMC4910146/ /pubmed/27153317 http://dx.doi.org/10.1021/acs.jctc.6b00299 Text en Copyright © 2016 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Gil-Ley, Alejandro
Bottaro, Sandro
Bussi, Giovanni
Empirical Corrections to the Amber RNA Force Field with Target Metadynamics
title Empirical Corrections to the Amber RNA Force Field with Target Metadynamics
title_full Empirical Corrections to the Amber RNA Force Field with Target Metadynamics
title_fullStr Empirical Corrections to the Amber RNA Force Field with Target Metadynamics
title_full_unstemmed Empirical Corrections to the Amber RNA Force Field with Target Metadynamics
title_short Empirical Corrections to the Amber RNA Force Field with Target Metadynamics
title_sort empirical corrections to the amber rna force field with target metadynamics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910146/
https://www.ncbi.nlm.nih.gov/pubmed/27153317
http://dx.doi.org/10.1021/acs.jctc.6b00299
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