Cargando…

Sodium or Not Sodium: Should Its Presence Affect the Accuracy of Pose Prediction in Docking GPCR Antagonists?

The function of the allosteric sodium ion in stabilizing the inactive form of GPCRs has been extensively described in the past decades. Its presence has been reported to be essential for the binding of antagonist molecules in the orthosteric site of these very important therapeutical targets. Among...

Descripción completa

Detalles Bibliográficos
Autores principales: Bassani, Davide, Pavan, Matteo, Sturlese, Mattia, Moro, Stefano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8950631/
https://www.ncbi.nlm.nih.gov/pubmed/35337144
http://dx.doi.org/10.3390/ph15030346
_version_ 1784675188686716928
author Bassani, Davide
Pavan, Matteo
Sturlese, Mattia
Moro, Stefano
author_facet Bassani, Davide
Pavan, Matteo
Sturlese, Mattia
Moro, Stefano
author_sort Bassani, Davide
collection PubMed
description The function of the allosteric sodium ion in stabilizing the inactive form of GPCRs has been extensively described in the past decades. Its presence has been reported to be essential for the binding of antagonist molecules in the orthosteric site of these very important therapeutical targets. Among the GPCR–antagonist crystal structures available, in most cases, the sodium ion could not be experimentally resolved, obliging computational scientists using GPCRs as targets for virtual screening to ask: “Should the sodium ion affect the accuracy of pose prediction in docking GPCR antagonists?” In the present study, we examined the performance of three orthogonal docking programs in the self-docking of GPCR antagonists to try to answer this question. The results of the present work highlight that if the sodium ion is resolved in the crystal structure used as the target, it should also be taken into account during the docking calculations. If the crystallographic studies were not able to resolve the sodium ion then no advantage would be obtained if this is manually inserted in the virtual target. The outcomes of the present analysis are useful for researchers exploiting molecular docking-based virtual screening to efficiently identify novel GPCR antagonists.
format Online
Article
Text
id pubmed-8950631
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-89506312022-03-26 Sodium or Not Sodium: Should Its Presence Affect the Accuracy of Pose Prediction in Docking GPCR Antagonists? Bassani, Davide Pavan, Matteo Sturlese, Mattia Moro, Stefano Pharmaceuticals (Basel) Article The function of the allosteric sodium ion in stabilizing the inactive form of GPCRs has been extensively described in the past decades. Its presence has been reported to be essential for the binding of antagonist molecules in the orthosteric site of these very important therapeutical targets. Among the GPCR–antagonist crystal structures available, in most cases, the sodium ion could not be experimentally resolved, obliging computational scientists using GPCRs as targets for virtual screening to ask: “Should the sodium ion affect the accuracy of pose prediction in docking GPCR antagonists?” In the present study, we examined the performance of three orthogonal docking programs in the self-docking of GPCR antagonists to try to answer this question. The results of the present work highlight that if the sodium ion is resolved in the crystal structure used as the target, it should also be taken into account during the docking calculations. If the crystallographic studies were not able to resolve the sodium ion then no advantage would be obtained if this is manually inserted in the virtual target. The outcomes of the present analysis are useful for researchers exploiting molecular docking-based virtual screening to efficiently identify novel GPCR antagonists. MDPI 2022-03-11 /pmc/articles/PMC8950631/ /pubmed/35337144 http://dx.doi.org/10.3390/ph15030346 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bassani, Davide
Pavan, Matteo
Sturlese, Mattia
Moro, Stefano
Sodium or Not Sodium: Should Its Presence Affect the Accuracy of Pose Prediction in Docking GPCR Antagonists?
title Sodium or Not Sodium: Should Its Presence Affect the Accuracy of Pose Prediction in Docking GPCR Antagonists?
title_full Sodium or Not Sodium: Should Its Presence Affect the Accuracy of Pose Prediction in Docking GPCR Antagonists?
title_fullStr Sodium or Not Sodium: Should Its Presence Affect the Accuracy of Pose Prediction in Docking GPCR Antagonists?
title_full_unstemmed Sodium or Not Sodium: Should Its Presence Affect the Accuracy of Pose Prediction in Docking GPCR Antagonists?
title_short Sodium or Not Sodium: Should Its Presence Affect the Accuracy of Pose Prediction in Docking GPCR Antagonists?
title_sort sodium or not sodium: should its presence affect the accuracy of pose prediction in docking gpcr antagonists?
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8950631/
https://www.ncbi.nlm.nih.gov/pubmed/35337144
http://dx.doi.org/10.3390/ph15030346
work_keys_str_mv AT bassanidavide sodiumornotsodiumshoulditspresenceaffecttheaccuracyofposepredictionindockinggpcrantagonists
AT pavanmatteo sodiumornotsodiumshoulditspresenceaffecttheaccuracyofposepredictionindockinggpcrantagonists
AT sturlesemattia sodiumornotsodiumshoulditspresenceaffecttheaccuracyofposepredictionindockinggpcrantagonists
AT morostefano sodiumornotsodiumshoulditspresenceaffecttheaccuracyofposepredictionindockinggpcrantagonists