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Molecular modeling, molecular dynamics simulation, and essential dynamics analysis of grancalcin: An upregulated biomarker in experimental autoimmune encephalomyelitis mice

The experimental autoimmune encephalomyelitis mouse model is the most commonly used animal model, and it best represents multiple sclerosis. Grancalcin (GCA) was discovered to be upregulated in EAE mice. GCA comprises 220 amino acids that have been assigned the UniprotKB ID Q8VC88. It is a calcium-b...

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Autores principales: Paul, Shamrat Kumar, Saddam, Md., Rahaman, Khandoker Asiqur, Choi, Jong-Gu, Lee, Sang-Suk, Hasan, Mahbub
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9626934/
https://www.ncbi.nlm.nih.gov/pubmed/36340004
http://dx.doi.org/10.1016/j.heliyon.2022.e11232
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author Paul, Shamrat Kumar
Saddam, Md.
Rahaman, Khandoker Asiqur
Choi, Jong-Gu
Lee, Sang-Suk
Hasan, Mahbub
author_facet Paul, Shamrat Kumar
Saddam, Md.
Rahaman, Khandoker Asiqur
Choi, Jong-Gu
Lee, Sang-Suk
Hasan, Mahbub
author_sort Paul, Shamrat Kumar
collection PubMed
description The experimental autoimmune encephalomyelitis mouse model is the most commonly used animal model, and it best represents multiple sclerosis. Grancalcin (GCA) was discovered to be upregulated in EAE mice. GCA comprises 220 amino acids that have been assigned the UniprotKB ID Q8VC88. It is a calcium-binding protein that helps neutrophils adhere to fibronectin and the formation of focal adhesions. However, the protein data bank does not contain the crystal structure of mouse GCA. The current study aims to analyze the structural and physicochemical properties of GCA. Mouse GCA showed a high percentage identity (87%) with the crystal structure of des (1–52) grancalcin with bound calcium (chain A) from Homo sapiens identified by its PDB id 1k94_A. Using the SWISS-MODEL server, we used 1k94_A as a template protein to model the mouse GCA protein. Compared to the template structure 1K94, three potential binding sites for calcium-binding have been proposed, ranging from 13 to 20, 80 to 91, and 109 to 120 amino acids. On an i5 personal computer with 8GB of RAM, GROMACS 2020.1 was utilized to run a 100 ns molecular dynamics (MD) simulation. RMSD, Rg, and RMSF analysis of an MD simulation trajectory indicate a stable and compact state throughout the simulation period of modeled proteins. We found that GCA is primarily alpha helical (Class 1), with eight alpha helices. The essential dynamics analysis captures PCA and SASA, culminating in the biological motions that correspond to the last 1000 frames. These findings will aid the development of potential inhibitors as well as the determination of binding pockets and residues for drug-like molecules.
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spelling pubmed-96269342022-11-03 Molecular modeling, molecular dynamics simulation, and essential dynamics analysis of grancalcin: An upregulated biomarker in experimental autoimmune encephalomyelitis mice Paul, Shamrat Kumar Saddam, Md. Rahaman, Khandoker Asiqur Choi, Jong-Gu Lee, Sang-Suk Hasan, Mahbub Heliyon Research Article The experimental autoimmune encephalomyelitis mouse model is the most commonly used animal model, and it best represents multiple sclerosis. Grancalcin (GCA) was discovered to be upregulated in EAE mice. GCA comprises 220 amino acids that have been assigned the UniprotKB ID Q8VC88. It is a calcium-binding protein that helps neutrophils adhere to fibronectin and the formation of focal adhesions. However, the protein data bank does not contain the crystal structure of mouse GCA. The current study aims to analyze the structural and physicochemical properties of GCA. Mouse GCA showed a high percentage identity (87%) with the crystal structure of des (1–52) grancalcin with bound calcium (chain A) from Homo sapiens identified by its PDB id 1k94_A. Using the SWISS-MODEL server, we used 1k94_A as a template protein to model the mouse GCA protein. Compared to the template structure 1K94, three potential binding sites for calcium-binding have been proposed, ranging from 13 to 20, 80 to 91, and 109 to 120 amino acids. On an i5 personal computer with 8GB of RAM, GROMACS 2020.1 was utilized to run a 100 ns molecular dynamics (MD) simulation. RMSD, Rg, and RMSF analysis of an MD simulation trajectory indicate a stable and compact state throughout the simulation period of modeled proteins. We found that GCA is primarily alpha helical (Class 1), with eight alpha helices. The essential dynamics analysis captures PCA and SASA, culminating in the biological motions that correspond to the last 1000 frames. These findings will aid the development of potential inhibitors as well as the determination of binding pockets and residues for drug-like molecules. Elsevier 2022-10-23 /pmc/articles/PMC9626934/ /pubmed/36340004 http://dx.doi.org/10.1016/j.heliyon.2022.e11232 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Paul, Shamrat Kumar
Saddam, Md.
Rahaman, Khandoker Asiqur
Choi, Jong-Gu
Lee, Sang-Suk
Hasan, Mahbub
Molecular modeling, molecular dynamics simulation, and essential dynamics analysis of grancalcin: An upregulated biomarker in experimental autoimmune encephalomyelitis mice
title Molecular modeling, molecular dynamics simulation, and essential dynamics analysis of grancalcin: An upregulated biomarker in experimental autoimmune encephalomyelitis mice
title_full Molecular modeling, molecular dynamics simulation, and essential dynamics analysis of grancalcin: An upregulated biomarker in experimental autoimmune encephalomyelitis mice
title_fullStr Molecular modeling, molecular dynamics simulation, and essential dynamics analysis of grancalcin: An upregulated biomarker in experimental autoimmune encephalomyelitis mice
title_full_unstemmed Molecular modeling, molecular dynamics simulation, and essential dynamics analysis of grancalcin: An upregulated biomarker in experimental autoimmune encephalomyelitis mice
title_short Molecular modeling, molecular dynamics simulation, and essential dynamics analysis of grancalcin: An upregulated biomarker in experimental autoimmune encephalomyelitis mice
title_sort molecular modeling, molecular dynamics simulation, and essential dynamics analysis of grancalcin: an upregulated biomarker in experimental autoimmune encephalomyelitis mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9626934/
https://www.ncbi.nlm.nih.gov/pubmed/36340004
http://dx.doi.org/10.1016/j.heliyon.2022.e11232
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