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How to Determine Accurate Conformational Ensembles by Metadynamics Metainference: A Chignolin Study Case
The reliability and usefulness of molecular dynamics simulations of equilibrium processes rests on their statistical precision and their capability to generate conformational ensembles in agreement with available experimental knowledge. Metadynamics Metainference (M&M), coupling molecular dynami...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187852/ https://www.ncbi.nlm.nih.gov/pubmed/34124166 http://dx.doi.org/10.3389/fmolb.2021.694130 |
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author | Paissoni, Cristina Camilloni, Carlo |
author_facet | Paissoni, Cristina Camilloni, Carlo |
author_sort | Paissoni, Cristina |
collection | PubMed |
description | The reliability and usefulness of molecular dynamics simulations of equilibrium processes rests on their statistical precision and their capability to generate conformational ensembles in agreement with available experimental knowledge. Metadynamics Metainference (M&M), coupling molecular dynamics with the enhanced sampling ability of Metadynamics and with the ability to integrate experimental information of Metainference, can in principle achieve both goals. Here we show that three different Metadynamics setups provide converged estimate of the populations of the three-states populated by a model peptide. Errors are estimated correctly by block averaging, but higher precision is obtained by performing independent replicates. One effect of Metadynamics is that of dramatically decreasing the number of effective frames resulting from the simulations and this is relevant for M&M where the number of replicas should be large enough to capture the conformational heterogeneity behind the experimental data. Our simulations allow also us to propose that monitoring the relative error associated with conformational averaging can help to determine the minimum number of replicas to be simulated in the context of M&M simulations. Altogether our data provides useful indication on how to generate sound conformational ensemble in agreement with experimental data. |
format | Online Article Text |
id | pubmed-8187852 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81878522021-06-10 How to Determine Accurate Conformational Ensembles by Metadynamics Metainference: A Chignolin Study Case Paissoni, Cristina Camilloni, Carlo Front Mol Biosci Molecular Biosciences The reliability and usefulness of molecular dynamics simulations of equilibrium processes rests on their statistical precision and their capability to generate conformational ensembles in agreement with available experimental knowledge. Metadynamics Metainference (M&M), coupling molecular dynamics with the enhanced sampling ability of Metadynamics and with the ability to integrate experimental information of Metainference, can in principle achieve both goals. Here we show that three different Metadynamics setups provide converged estimate of the populations of the three-states populated by a model peptide. Errors are estimated correctly by block averaging, but higher precision is obtained by performing independent replicates. One effect of Metadynamics is that of dramatically decreasing the number of effective frames resulting from the simulations and this is relevant for M&M where the number of replicas should be large enough to capture the conformational heterogeneity behind the experimental data. Our simulations allow also us to propose that monitoring the relative error associated with conformational averaging can help to determine the minimum number of replicas to be simulated in the context of M&M simulations. Altogether our data provides useful indication on how to generate sound conformational ensemble in agreement with experimental data. Frontiers Media S.A. 2021-05-26 /pmc/articles/PMC8187852/ /pubmed/34124166 http://dx.doi.org/10.3389/fmolb.2021.694130 Text en Copyright © 2021 Paissoni and Camilloni. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Molecular Biosciences Paissoni, Cristina Camilloni, Carlo How to Determine Accurate Conformational Ensembles by Metadynamics Metainference: A Chignolin Study Case |
title | How to Determine Accurate Conformational Ensembles by Metadynamics Metainference: A Chignolin Study Case |
title_full | How to Determine Accurate Conformational Ensembles by Metadynamics Metainference: A Chignolin Study Case |
title_fullStr | How to Determine Accurate Conformational Ensembles by Metadynamics Metainference: A Chignolin Study Case |
title_full_unstemmed | How to Determine Accurate Conformational Ensembles by Metadynamics Metainference: A Chignolin Study Case |
title_short | How to Determine Accurate Conformational Ensembles by Metadynamics Metainference: A Chignolin Study Case |
title_sort | how to determine accurate conformational ensembles by metadynamics metainference: a chignolin study case |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187852/ https://www.ncbi.nlm.nih.gov/pubmed/34124166 http://dx.doi.org/10.3389/fmolb.2021.694130 |
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