Ligand binding: evaluating the contribution of the water molecules network using the Fragment Molecular Orbital method

Water molecules play a crucial role in protein–ligand binding, and many tools exist that aim to predict the position and relative energies of these important, but challenging participants of biomolecular recognition. The available tools are, in general, capable of predicting the location of water mo...

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Detalles Bibliográficos
Autores principales: Lukac, Iva, Wyatt, Paul G., Gilbert, Ian H., Zuccotto, Fabio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8523014/
https://www.ncbi.nlm.nih.gov/pubmed/34458939
http://dx.doi.org/10.1007/s10822-021-00416-3
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author Lukac, Iva
Wyatt, Paul G.
Gilbert, Ian H.
Zuccotto, Fabio
author_facet Lukac, Iva
Wyatt, Paul G.
Gilbert, Ian H.
Zuccotto, Fabio
author_sort Lukac, Iva
collection PubMed
description Water molecules play a crucial role in protein–ligand binding, and many tools exist that aim to predict the position and relative energies of these important, but challenging participants of biomolecular recognition. The available tools are, in general, capable of predicting the location of water molecules. However, predicting the effects of their displacement is still very challenging. In this work, a linear-scaling quantum mechanics-based approach was used to assess water network energetics and the changes in network stability upon ligand structural modifications. This approach offers a valuable way to improve understanding of SAR data and help guide compound design. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10822-021-00416-3.
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spelling pubmed-85230142021-10-22 Ligand binding: evaluating the contribution of the water molecules network using the Fragment Molecular Orbital method Lukac, Iva Wyatt, Paul G. Gilbert, Ian H. Zuccotto, Fabio J Comput Aided Mol Des Article Water molecules play a crucial role in protein–ligand binding, and many tools exist that aim to predict the position and relative energies of these important, but challenging participants of biomolecular recognition. The available tools are, in general, capable of predicting the location of water molecules. However, predicting the effects of their displacement is still very challenging. In this work, a linear-scaling quantum mechanics-based approach was used to assess water network energetics and the changes in network stability upon ligand structural modifications. This approach offers a valuable way to improve understanding of SAR data and help guide compound design. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10822-021-00416-3. Springer International Publishing 2021-08-30 2021 /pmc/articles/PMC8523014/ /pubmed/34458939 http://dx.doi.org/10.1007/s10822-021-00416-3 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
Lukac, Iva
Wyatt, Paul G.
Gilbert, Ian H.
Zuccotto, Fabio
Ligand binding: evaluating the contribution of the water molecules network using the Fragment Molecular Orbital method
title Ligand binding: evaluating the contribution of the water molecules network using the Fragment Molecular Orbital method
title_full Ligand binding: evaluating the contribution of the water molecules network using the Fragment Molecular Orbital method
title_fullStr Ligand binding: evaluating the contribution of the water molecules network using the Fragment Molecular Orbital method
title_full_unstemmed Ligand binding: evaluating the contribution of the water molecules network using the Fragment Molecular Orbital method
title_short Ligand binding: evaluating the contribution of the water molecules network using the Fragment Molecular Orbital method
title_sort ligand binding: evaluating the contribution of the water molecules network using the fragment molecular orbital method
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8523014/
https://www.ncbi.nlm.nih.gov/pubmed/34458939
http://dx.doi.org/10.1007/s10822-021-00416-3
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