Cargando…
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...
Autores principales: | , , |
---|---|
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 |
_version_ | 1782437959609352192 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4910146 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | American
Chemical Society |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT gilleyalejandro empiricalcorrectionstotheamberrnaforcefieldwithtargetmetadynamics AT bottarosandro empiricalcorrectionstotheamberrnaforcefieldwithtargetmetadynamics AT bussigiovanni empiricalcorrectionstotheamberrnaforcefieldwithtargetmetadynamics |