Binding free energies for the SAMPL8 CB8 “Drugs of Abuse” challenge from umbrella sampling combined with Hamiltonian replica exchange

Umbrella sampling along a one-dimensional order parameter in combination with Hamiltonian replica exchange was employed to calculate the binding free energy of five guest molecules with known affinity to cucurbit[8]uril. A simple empirical approach correcting for the overestimation of the affinity b...

Descripción completa

Detalles Bibliográficos
Autores principales: Markthaler, Daniel, Kraus, Hamzeh, Hansen, Niels
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8831271/
https://www.ncbi.nlm.nih.gov/pubmed/34978001
http://dx.doi.org/10.1007/s10822-021-00439-w
_version_ 1784648469358575616
author Markthaler, Daniel
Kraus, Hamzeh
Hansen, Niels
author_facet Markthaler, Daniel
Kraus, Hamzeh
Hansen, Niels
author_sort Markthaler, Daniel
collection PubMed
description Umbrella sampling along a one-dimensional order parameter in combination with Hamiltonian replica exchange was employed to calculate the binding free energy of five guest molecules with known affinity to cucurbit[8]uril. A simple empirical approach correcting for the overestimation of the affinity by the GAFF force field was proposed and subsequently applied to the seven guest molecules of the “Drugs of Abuse” SAMPL8 challenge. Compared to the uncorrected binding free energies, the systematic error decreased but quantitative agreement with experiment was only reached for a few compounds. From a retrospective analysis a weak point of the correction term was identified. SUPPLEMENTARY INFORMATION: The online version of this article contains supplementary material available 10.1007/s10822-021-00439-w.
format Online
Article
Text
id pubmed-8831271
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Springer International Publishing
record_format MEDLINE/PubMed
spelling pubmed-88312712022-02-23 Binding free energies for the SAMPL8 CB8 “Drugs of Abuse” challenge from umbrella sampling combined with Hamiltonian replica exchange Markthaler, Daniel Kraus, Hamzeh Hansen, Niels J Comput Aided Mol Des Article Umbrella sampling along a one-dimensional order parameter in combination with Hamiltonian replica exchange was employed to calculate the binding free energy of five guest molecules with known affinity to cucurbit[8]uril. A simple empirical approach correcting for the overestimation of the affinity by the GAFF force field was proposed and subsequently applied to the seven guest molecules of the “Drugs of Abuse” SAMPL8 challenge. Compared to the uncorrected binding free energies, the systematic error decreased but quantitative agreement with experiment was only reached for a few compounds. From a retrospective analysis a weak point of the correction term was identified. SUPPLEMENTARY INFORMATION: The online version of this article contains supplementary material available 10.1007/s10822-021-00439-w. Springer International Publishing 2022-01-03 2022 /pmc/articles/PMC8831271/ /pubmed/34978001 http://dx.doi.org/10.1007/s10822-021-00439-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Markthaler, Daniel
Kraus, Hamzeh
Hansen, Niels
Binding free energies for the SAMPL8 CB8 “Drugs of Abuse” challenge from umbrella sampling combined with Hamiltonian replica exchange
title Binding free energies for the SAMPL8 CB8 “Drugs of Abuse” challenge from umbrella sampling combined with Hamiltonian replica exchange
title_full Binding free energies for the SAMPL8 CB8 “Drugs of Abuse” challenge from umbrella sampling combined with Hamiltonian replica exchange
title_fullStr Binding free energies for the SAMPL8 CB8 “Drugs of Abuse” challenge from umbrella sampling combined with Hamiltonian replica exchange
title_full_unstemmed Binding free energies for the SAMPL8 CB8 “Drugs of Abuse” challenge from umbrella sampling combined with Hamiltonian replica exchange
title_short Binding free energies for the SAMPL8 CB8 “Drugs of Abuse” challenge from umbrella sampling combined with Hamiltonian replica exchange
title_sort binding free energies for the sampl8 cb8 “drugs of abuse” challenge from umbrella sampling combined with hamiltonian replica exchange
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8831271/
https://www.ncbi.nlm.nih.gov/pubmed/34978001
http://dx.doi.org/10.1007/s10822-021-00439-w
work_keys_str_mv AT markthalerdaniel bindingfreeenergiesforthesampl8cb8drugsofabusechallengefromumbrellasamplingcombinedwithhamiltonianreplicaexchange
AT kraushamzeh bindingfreeenergiesforthesampl8cb8drugsofabusechallengefromumbrellasamplingcombinedwithhamiltonianreplicaexchange
AT hansenniels bindingfreeenergiesforthesampl8cb8drugsofabusechallengefromumbrellasamplingcombinedwithhamiltonianreplicaexchange

Ejemplares similares