Autoencoder-based detection of the residues involved in G protein-coupled receptor signaling

Abstract Regulator binding and mutations alter protein dynamics. The transmission of the signal of these alterations to distant sites through protein motion results in changes in protein expression and cell function. The detection of residues involved in signal transmission contributes to an elucida...

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Autores principales:	Yuko Tsuchiya, Kei Taneishi, Yasushige Yonezawa
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/932d74c13585440eb9ce44561746141e
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spelling	oai:doaj.org-article:932d74c13585440eb9ce44561746141e2021-12-02T18:01:48ZAutoencoder-based detection of the residues involved in G protein-coupled receptor signaling10.1038/s41598-021-99019-z2045-2322https://doaj.org/article/932d74c13585440eb9ce44561746141e2021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99019-zhttps://doaj.org/toc/2045-2322Abstract Regulator binding and mutations alter protein dynamics. The transmission of the signal of these alterations to distant sites through protein motion results in changes in protein expression and cell function. The detection of residues involved in signal transmission contributes to an elucidation of the mechanisms underlying processes as vast as cellular function and disease pathogenesis. We developed an autoencoder (AE) based method that detects residues essential for signaling by comparing the fluctuation data, particularly the time fluctuation of the side-chain distances between residues, during molecular dynamics simulations between the ligand-bound and -unbound forms or wild-type and mutant forms of proteins. Here, the AE-based method was applied to the G protein-coupled receptor (GPCR) system, particularly a class A-type GPCR, CXCR4, to detect the essential residues involved in signaling. Among the residues involved in the signaling of the homolog CXCR2, which were extracted from the literature based on the complex structures of the ligand and G protein, our method could detect more than half of the essential residues involved in G protein signaling, including those spanning the fifth and sixth transmembrane helices in the intracellular region, despite the lack of information regarding the interaction with G protein in our CXCR4 models.Yuko TsuchiyaKei TaneishiYasushige YonezawaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yuko Tsuchiya Kei Taneishi Yasushige Yonezawa Autoencoder-based detection of the residues involved in G protein-coupled receptor signaling
description	Abstract Regulator binding and mutations alter protein dynamics. The transmission of the signal of these alterations to distant sites through protein motion results in changes in protein expression and cell function. The detection of residues involved in signal transmission contributes to an elucidation of the mechanisms underlying processes as vast as cellular function and disease pathogenesis. We developed an autoencoder (AE) based method that detects residues essential for signaling by comparing the fluctuation data, particularly the time fluctuation of the side-chain distances between residues, during molecular dynamics simulations between the ligand-bound and -unbound forms or wild-type and mutant forms of proteins. Here, the AE-based method was applied to the G protein-coupled receptor (GPCR) system, particularly a class A-type GPCR, CXCR4, to detect the essential residues involved in signaling. Among the residues involved in the signaling of the homolog CXCR2, which were extracted from the literature based on the complex structures of the ligand and G protein, our method could detect more than half of the essential residues involved in G protein signaling, including those spanning the fifth and sixth transmembrane helices in the intracellular region, despite the lack of information regarding the interaction with G protein in our CXCR4 models.
format	article
author	Yuko Tsuchiya Kei Taneishi Yasushige Yonezawa
author_facet	Yuko Tsuchiya Kei Taneishi Yasushige Yonezawa
author_sort	Yuko Tsuchiya
title	Autoencoder-based detection of the residues involved in G protein-coupled receptor signaling
title_short	Autoencoder-based detection of the residues involved in G protein-coupled receptor signaling
title_full	Autoencoder-based detection of the residues involved in G protein-coupled receptor signaling
title_fullStr	Autoencoder-based detection of the residues involved in G protein-coupled receptor signaling
title_full_unstemmed	Autoencoder-based detection of the residues involved in G protein-coupled receptor signaling
title_sort	autoencoder-based detection of the residues involved in g protein-coupled receptor signaling
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/932d74c13585440eb9ce44561746141e
work_keys_str_mv	AT yukotsuchiya autoencoderbaseddetectionoftheresiduesinvolvedingproteincoupledreceptorsignaling AT keitaneishi autoencoderbaseddetectionoftheresiduesinvolvedingproteincoupledreceptorsignaling AT yasushigeyonezawa autoencoderbaseddetectionoftheresiduesinvolvedingproteincoupledreceptorsignaling
_version_	1718378941521068032

Autoencoder-based detection of the residues involved in G protein-coupled receptor signaling

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