Cryptic pocket formation underlies allosteric modulator selectivity at muscarinic GPCRs

Allosteric GPCR modulators can achieve exquisite subtype selectivity, but the underlying mechanism is unclear. Using molecular dynamics simulations, the authors here identify a previously undetected dynamic pocket in muscarinic GPCRs that is critical for subtype selectivity of allosteric modulators.

Guardado en:

Detalles Bibliográficos
Autores principales:	Scott A. Hollingsworth, Brendan Kelly, Celine Valant, Jordan Arthur Michaelis, Olivia Mastromihalis, Geoff Thompson, A. J. Venkatakrishnan, Samuel Hertig, Peter J. Scammells, Patrick M. Sexton, Christian C. Felder, Arthur Christopoulos, Ron O. Dror
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Science Q
Acceso en línea:	https://doaj.org/article/a0e90ef319f249dd8f9b3fd6b23a0233
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a0e90ef319f249dd8f9b3fd6b23a0233
record_format	dspace
spelling	oai:doaj.org-article:a0e90ef319f249dd8f9b3fd6b23a02332021-12-02T15:35:03ZCryptic pocket formation underlies allosteric modulator selectivity at muscarinic GPCRs10.1038/s41467-019-11062-72041-1723https://doaj.org/article/a0e90ef319f249dd8f9b3fd6b23a02332019-07-01T00:00:00Zhttps://doi.org/10.1038/s41467-019-11062-7https://doaj.org/toc/2041-1723Allosteric GPCR modulators can achieve exquisite subtype selectivity, but the underlying mechanism is unclear. Using molecular dynamics simulations, the authors here identify a previously undetected dynamic pocket in muscarinic GPCRs that is critical for subtype selectivity of allosteric modulators.Scott A. HollingsworthBrendan KellyCeline ValantJordan Arthur MichaelisOlivia MastromihalisGeoff ThompsonA. J. VenkatakrishnanSamuel HertigPeter J. ScammellsPatrick M. SextonChristian C. FelderArthur ChristopoulosRon O. DrorNature PortfolioarticleScienceQENNature Communications, Vol 10, Iss 1, Pp 1-9 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Science Q
spellingShingle	Science Q Scott A. Hollingsworth Brendan Kelly Celine Valant Jordan Arthur Michaelis Olivia Mastromihalis Geoff Thompson A. J. Venkatakrishnan Samuel Hertig Peter J. Scammells Patrick M. Sexton Christian C. Felder Arthur Christopoulos Ron O. Dror Cryptic pocket formation underlies allosteric modulator selectivity at muscarinic GPCRs
description	Allosteric GPCR modulators can achieve exquisite subtype selectivity, but the underlying mechanism is unclear. Using molecular dynamics simulations, the authors here identify a previously undetected dynamic pocket in muscarinic GPCRs that is critical for subtype selectivity of allosteric modulators.
format	article
author	Scott A. Hollingsworth Brendan Kelly Celine Valant Jordan Arthur Michaelis Olivia Mastromihalis Geoff Thompson A. J. Venkatakrishnan Samuel Hertig Peter J. Scammells Patrick M. Sexton Christian C. Felder Arthur Christopoulos Ron O. Dror
author_facet	Scott A. Hollingsworth Brendan Kelly Celine Valant Jordan Arthur Michaelis Olivia Mastromihalis Geoff Thompson A. J. Venkatakrishnan Samuel Hertig Peter J. Scammells Patrick M. Sexton Christian C. Felder Arthur Christopoulos Ron O. Dror
author_sort	Scott A. Hollingsworth
title	Cryptic pocket formation underlies allosteric modulator selectivity at muscarinic GPCRs
title_short	Cryptic pocket formation underlies allosteric modulator selectivity at muscarinic GPCRs
title_full	Cryptic pocket formation underlies allosteric modulator selectivity at muscarinic GPCRs
title_fullStr	Cryptic pocket formation underlies allosteric modulator selectivity at muscarinic GPCRs
title_full_unstemmed	Cryptic pocket formation underlies allosteric modulator selectivity at muscarinic GPCRs
title_sort	cryptic pocket formation underlies allosteric modulator selectivity at muscarinic gpcrs
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/a0e90ef319f249dd8f9b3fd6b23a0233
work_keys_str_mv	AT scottahollingsworth crypticpocketformationunderliesallostericmodulatorselectivityatmuscarinicgpcrs AT brendankelly crypticpocketformationunderliesallostericmodulatorselectivityatmuscarinicgpcrs AT celinevalant crypticpocketformationunderliesallostericmodulatorselectivityatmuscarinicgpcrs AT jordanarthurmichaelis crypticpocketformationunderliesallostericmodulatorselectivityatmuscarinicgpcrs AT oliviamastromihalis crypticpocketformationunderliesallostericmodulatorselectivityatmuscarinicgpcrs AT geoffthompson crypticpocketformationunderliesallostericmodulatorselectivityatmuscarinicgpcrs AT ajvenkatakrishnan crypticpocketformationunderliesallostericmodulatorselectivityatmuscarinicgpcrs AT samuelhertig crypticpocketformationunderliesallostericmodulatorselectivityatmuscarinicgpcrs AT peterjscammells crypticpocketformationunderliesallostericmodulatorselectivityatmuscarinicgpcrs AT patrickmsexton crypticpocketformationunderliesallostericmodulatorselectivityatmuscarinicgpcrs AT christiancfelder crypticpocketformationunderliesallostericmodulatorselectivityatmuscarinicgpcrs AT arthurchristopoulos crypticpocketformationunderliesallostericmodulatorselectivityatmuscarinicgpcrs AT ronodror crypticpocketformationunderliesallostericmodulatorselectivityatmuscarinicgpcrs
_version_	1718386674004656128

Cryptic pocket formation underlies allosteric modulator selectivity at muscarinic GPCRs

Ejemplares similares