How Do Molecular Dynamics Data Complement Static Structural Data of GPCRs

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2020 Aug 23

PMID 32824756

Citations 15

Authors

Mariona Torrens-Fontanals

Tomasz Maciej Stepniewski

David Aranda-Garcia

Adrian Morales-Pastor

Brian Medel-Lacruz

Jana Selent

Affiliations

Soon will be listed here.

Abstract

G protein-coupled receptors (GPCRs) are implicated in nearly every physiological process in the human body and therefore represent an important drug targeting class. Advances in X-ray crystallography and cryo-electron microscopy (cryo-EM) have provided multiple static structures of GPCRs in complex with various signaling partners. However, GPCR functionality is largely determined by their flexibility and ability to transition between distinct structural conformations. Due to this dynamic nature, a static snapshot does not fully explain the complexity of GPCR signal transduction. Molecular dynamics (MD) simulations offer the opportunity to simulate the structural motions of biological processes at atomic resolution. Thus, this technique can incorporate the missing information on protein flexibility into experimentally solved structures. Here, we review the contribution of MD simulations to complement static structural data and to improve our understanding of GPCR physiology and pharmacology, as well as the challenges that still need to be overcome to reach the full potential of this technique.

Citing Articles

Large scale investigation of GPCR molecular dynamics data uncovers allosteric sites and lateral gateways.

Aranda-Garcia D, Stepniewski T, Torrens-Fontanals M, Garcia-Recio A, Lopez-Balastegui M, Medel-Lacruz B Nat Commun. 2025; 16(1):2020.

PMID: 40016203 PMC: 11868581. DOI: 10.1038/s41467-025-57034-y.

Exploring the Binding Mechanism of ADGRG2 Through Metadynamics and Biochemical Analysis.

Zhang C, Zhang R, Qi Y, Wen X, Sun J, Xiao P Int J Mol Sci. 2025; 26(1.

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G protein-specific mechanisms in the serotonin 5-HT receptor regulate psychosis-related effects and memory deficits.

Kossatz E, Diez-Alarcia R, Gaitonde S, Ramon-Duaso C, Stepniewski T, Aranda-Garcia D Nat Commun. 2024; 15(1):4307.

PMID: 38811567 PMC: 11137019. DOI: 10.1038/s41467-024-48196-2.

Unravelling the mechanism of neurotensin recognition by neurotensin receptor 1.

Asadollahi K, Rajput S, de Zhang L, Ang C, Nie S, Williamson N Nat Commun. 2023; 14(1):8155.

PMID: 38071229 PMC: 10710507. DOI: 10.1038/s41467-023-44010-7.

GPCR molecular dynamics forecasting using recurrent neural networks.

Lopez-Correa J, Konig C, Vellido A Sci Rep. 2023; 13(1):20995.

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