Autoencoder-based detection of the residues involved in G protein-coupled receptor signaling
| Autor: | Kei Taneishi, Yuko Tsuchiya, Yasushige Yonezawa |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular Protein Conformation G protein Science Amino Acid Motifs Mutant Quantitative Structure-Activity Relationship Molecular Dynamics Simulation Protein function predictions Ligands Article Receptors G-Protein-Coupled Computational biophysics Machine learning Humans Protein Interaction Domains and Motifs G protein-coupled receptor Binding Sites Multidisciplinary Chemistry Protein dynamics Computational Biology Ligand (biochemistry) G Protein-Coupled Receptor Signaling Computational biology and bioinformatics Cell biology Molecular Docking Simulation Transmembrane domain Medicine Function (biology) Protein Binding |
| Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-9 (2021) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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