Next Article in Journal
Formulation of Chitosan-Coated Brigatinib Nanospanlastics: Optimization, Characterization, Stability Assessment and In-Vitro Cytotoxicity Activity against H-1975 Cell Lines
Next Article in Special Issue
Special Issue “GPCRs: Ligands and beyond 2022”
Previous Article in Journal
Efficacy of Adaptogens in Patients with Long COVID-19: A Randomized, Quadruple-Blind, Placebo-Controlled Trial
Previous Article in Special Issue
Ligands and Beyond: Mechanosensitive Adhesion GPCRs
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

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

Molecular Modeling Section (MMS), Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2022, 15(3), 346; https://doi.org/10.3390/ph15030346
Submission received: 9 February 2022 / Revised: 2 March 2022 / Accepted: 9 March 2022 / Published: 11 March 2022
(This article belongs to the Special Issue GPCRs: Ligands and beyond 2022)

Abstract

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.
Keywords: GPCR; molecular docking; sodium ion; allosteric modulator; antagonist; benchmark; performance; GOLD; PLANTS; Glide GPCR; molecular docking; sodium ion; allosteric modulator; antagonist; benchmark; performance; GOLD; PLANTS; Glide
Graphical Abstract

Share and Cite

MDPI and ACS Style

Bassani, D.; Pavan, M.; Sturlese, M.; Moro, S. Sodium or Not Sodium: Should Its Presence Affect the Accuracy of Pose Prediction in Docking GPCR Antagonists? Pharmaceuticals 2022, 15, 346. https://doi.org/10.3390/ph15030346

AMA Style

Bassani D, Pavan M, Sturlese M, Moro S. Sodium or Not Sodium: Should Its Presence Affect the Accuracy of Pose Prediction in Docking GPCR Antagonists? Pharmaceuticals. 2022; 15(3):346. https://doi.org/10.3390/ph15030346

Chicago/Turabian Style

Bassani, Davide, Matteo Pavan, Mattia Sturlese, and Stefano Moro. 2022. "Sodium or Not Sodium: Should Its Presence Affect the Accuracy of Pose Prediction in Docking GPCR Antagonists?" Pharmaceuticals 15, no. 3: 346. https://doi.org/10.3390/ph15030346

APA Style

Bassani, D., Pavan, M., Sturlese, M., & Moro, S. (2022). Sodium or Not Sodium: Should Its Presence Affect the Accuracy of Pose Prediction in Docking GPCR Antagonists? Pharmaceuticals, 15(3), 346. https://doi.org/10.3390/ph15030346

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop