Autoencoder-based detection of the residues involved in G protein-coupled receptor signaling.
Sci Rep
; 11(1): 19867, 2021 10 06.
Article
en En
| MEDLINE
| ID: mdl-34615896
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sitios de Unión
/
Modelos Moleculares
/
Biología Computacional
/
Secuencias de Aminoácidos
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Relación Estructura-Actividad Cuantitativa
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Receptores Acoplados a Proteínas G
/
Dominios y Motivos de Interacción de Proteínas
Tipo de estudio:
Diagnostic_studies
Límite:
Humans
Idioma:
En
Revista:
Sci Rep
Año:
2021
Tipo del documento:
Article
País de afiliación:
Japón