Cargando…
The role of water in host-guest interaction
One of the main applications of atomistic computer simulations is the calculation of ligand binding free energies. The accuracy of these calculations depends on the force field quality and on the thoroughness of configuration sampling. Sampling is an obstacle in simulations due to the frequent appea...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782548/ https://www.ncbi.nlm.nih.gov/pubmed/33397926 http://dx.doi.org/10.1038/s41467-020-20310-0 |
_version_ | 1783631928492032000 |
---|---|
author | Rizzi, Valerio Bonati, Luigi Ansari, Narjes Parrinello, Michele |
author_facet | Rizzi, Valerio Bonati, Luigi Ansari, Narjes Parrinello, Michele |
author_sort | Rizzi, Valerio |
collection | PubMed |
description | One of the main applications of atomistic computer simulations is the calculation of ligand binding free energies. The accuracy of these calculations depends on the force field quality and on the thoroughness of configuration sampling. Sampling is an obstacle in simulations due to the frequent appearance of kinetic bottlenecks in the free energy landscape. Very often this difficulty is circumvented by enhanced sampling techniques. Typically, these techniques depend on the introduction of appropriate collective variables that are meant to capture the system’s degrees of freedom. In ligand binding, water has long been known to play a key role, but its complex behaviour has proven difficult to fully capture. In this paper we combine machine learning with physical intuition to build a non-local and highly efficient water-describing collective variable. We use it to study a set of host-guest systems from the SAMPL5 challenge. We obtain highly accurate binding free energies and good agreement with experiments. The role of water during the binding process is then analysed in some detail. |
format | Online Article Text |
id | pubmed-7782548 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-77825482021-01-11 The role of water in host-guest interaction Rizzi, Valerio Bonati, Luigi Ansari, Narjes Parrinello, Michele Nat Commun Article One of the main applications of atomistic computer simulations is the calculation of ligand binding free energies. The accuracy of these calculations depends on the force field quality and on the thoroughness of configuration sampling. Sampling is an obstacle in simulations due to the frequent appearance of kinetic bottlenecks in the free energy landscape. Very often this difficulty is circumvented by enhanced sampling techniques. Typically, these techniques depend on the introduction of appropriate collective variables that are meant to capture the system’s degrees of freedom. In ligand binding, water has long been known to play a key role, but its complex behaviour has proven difficult to fully capture. In this paper we combine machine learning with physical intuition to build a non-local and highly efficient water-describing collective variable. We use it to study a set of host-guest systems from the SAMPL5 challenge. We obtain highly accurate binding free energies and good agreement with experiments. The role of water during the binding process is then analysed in some detail. Nature Publishing Group UK 2021-01-04 /pmc/articles/PMC7782548/ /pubmed/33397926 http://dx.doi.org/10.1038/s41467-020-20310-0 Text en © The Author(s) 2021 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Rizzi, Valerio Bonati, Luigi Ansari, Narjes Parrinello, Michele The role of water in host-guest interaction |
title | The role of water in host-guest interaction |
title_full | The role of water in host-guest interaction |
title_fullStr | The role of water in host-guest interaction |
title_full_unstemmed | The role of water in host-guest interaction |
title_short | The role of water in host-guest interaction |
title_sort | role of water in host-guest interaction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782548/ https://www.ncbi.nlm.nih.gov/pubmed/33397926 http://dx.doi.org/10.1038/s41467-020-20310-0 |
work_keys_str_mv | AT rizzivalerio theroleofwaterinhostguestinteraction AT bonatiluigi theroleofwaterinhostguestinteraction AT ansarinarjes theroleofwaterinhostguestinteraction AT parrinellomichele theroleofwaterinhostguestinteraction AT rizzivalerio roleofwaterinhostguestinteraction AT bonatiluigi roleofwaterinhostguestinteraction AT ansarinarjes roleofwaterinhostguestinteraction AT parrinellomichele roleofwaterinhostguestinteraction |