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Non-equilibrium approach for binding free energies in cyclodextrins in SAMPL7: force fields and software
In the current work we report on our participation in the SAMPL7 challenge calculating absolute free energies of the host–guest systems, where 2 guest molecules were probed against 9 hosts-cyclodextrin and its derivatives. Our submission was based on the non-equilibrium free energy calculation proto...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862541/ https://www.ncbi.nlm.nih.gov/pubmed/33230742 http://dx.doi.org/10.1007/s10822-020-00359-1 |
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author | Khalak, Yuriy Tresadern, Gary de Groot, Bert L. Gapsys, Vytautas |
author_facet | Khalak, Yuriy Tresadern, Gary de Groot, Bert L. Gapsys, Vytautas |
author_sort | Khalak, Yuriy |
collection | PubMed |
description | In the current work we report on our participation in the SAMPL7 challenge calculating absolute free energies of the host–guest systems, where 2 guest molecules were probed against 9 hosts-cyclodextrin and its derivatives. Our submission was based on the non-equilibrium free energy calculation protocol utilizing an averaged consensus result from two force fields (GAFF and CGenFF). The submitted prediction achieved accuracy of [Formula: see text] in terms of the unsigned error averaged over the whole dataset. Subsequently, we further report on the underlying reasons for discrepancies between our calculations and another submission to the SAMPL7 challenge which employed a similar methodology, but disparate ligand and water force fields. As a result we have uncovered a number of issues in the dihedral parameter definition of the GAFF 2 force field. In addition, we identified particular cases in the molecular topologies where different software packages had a different interpretation of the same force field. This latter observation might be of particular relevance for systematic comparisons of molecular simulation software packages. The aforementioned factors have an influence on the final free energy estimates and need to be considered when performing alchemical calculations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10822-020-00359-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-7862541 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-78625412021-02-16 Non-equilibrium approach for binding free energies in cyclodextrins in SAMPL7: force fields and software Khalak, Yuriy Tresadern, Gary de Groot, Bert L. Gapsys, Vytautas J Comput Aided Mol Des Article In the current work we report on our participation in the SAMPL7 challenge calculating absolute free energies of the host–guest systems, where 2 guest molecules were probed against 9 hosts-cyclodextrin and its derivatives. Our submission was based on the non-equilibrium free energy calculation protocol utilizing an averaged consensus result from two force fields (GAFF and CGenFF). The submitted prediction achieved accuracy of [Formula: see text] in terms of the unsigned error averaged over the whole dataset. Subsequently, we further report on the underlying reasons for discrepancies between our calculations and another submission to the SAMPL7 challenge which employed a similar methodology, but disparate ligand and water force fields. As a result we have uncovered a number of issues in the dihedral parameter definition of the GAFF 2 force field. In addition, we identified particular cases in the molecular topologies where different software packages had a different interpretation of the same force field. This latter observation might be of particular relevance for systematic comparisons of molecular simulation software packages. The aforementioned factors have an influence on the final free energy estimates and need to be considered when performing alchemical calculations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10822-020-00359-1) contains supplementary material, which is available to authorized users. Springer International Publishing 2020-11-24 2021 /pmc/articles/PMC7862541/ /pubmed/33230742 http://dx.doi.org/10.1007/s10822-020-00359-1 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Khalak, Yuriy Tresadern, Gary de Groot, Bert L. Gapsys, Vytautas Non-equilibrium approach for binding free energies in cyclodextrins in SAMPL7: force fields and software |
title | Non-equilibrium approach for binding free energies in cyclodextrins in SAMPL7: force fields and software |
title_full | Non-equilibrium approach for binding free energies in cyclodextrins in SAMPL7: force fields and software |
title_fullStr | Non-equilibrium approach for binding free energies in cyclodextrins in SAMPL7: force fields and software |
title_full_unstemmed | Non-equilibrium approach for binding free energies in cyclodextrins in SAMPL7: force fields and software |
title_short | Non-equilibrium approach for binding free energies in cyclodextrins in SAMPL7: force fields and software |
title_sort | non-equilibrium approach for binding free energies in cyclodextrins in sampl7: force fields and software |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862541/ https://www.ncbi.nlm.nih.gov/pubmed/33230742 http://dx.doi.org/10.1007/s10822-020-00359-1 |
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