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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Main Authors: Shamrat Kumar Paul, Md. Saddam, Khandoker Asiqur Rahaman, Jong-Gu Choi, Sang-Suk Lee, Mahbub Hasan
Format: Article
Language:English
Published: Elsevier 2022-10-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844022025208
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author Shamrat Kumar Paul
Md. Saddam
Khandoker Asiqur Rahaman
Jong-Gu Choi
Sang-Suk Lee
Mahbub Hasan
author_facet Shamrat Kumar Paul
Md. Saddam
Khandoker Asiqur Rahaman
Jong-Gu Choi
Sang-Suk Lee
Mahbub Hasan
author_sort Shamrat Kumar Paul
collection DOAJ
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 doaj.art-27dc523d750940609b591beff742e3052022-12-22T03:56:25ZengElsevierHeliyon2405-84402022-10-01810e11232Molecular modeling, molecular dynamics simulation, and essential dynamics analysis of grancalcin: An upregulated biomarker in experimental autoimmune encephalomyelitis miceShamrat Kumar Paul0Md. Saddam1Khandoker Asiqur Rahaman2Jong-Gu Choi3Sang-Suk Lee4Mahbub Hasan5Department of Biochemistry and Molecular Biology, Life Science Faculty, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, BangladeshDepartment of Biochemistry and Molecular Biology, Life Science Faculty, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, BangladeshDivision of Biomedical Science and Technology, KIST-School, Korea University of Science and Technology, Seoul 02792, South KoreaDepartment of Oriental Biomedical Engineering, Sangji University, Wonju 26339, South KoreaDepartment of Oriental Biomedical Engineering, Sangji University, Wonju 26339, South Korea; Corresponding author.Department of Biochemistry and Molecular Biology, Life Science Faculty, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh; Department of Oriental Biomedical Engineering, Sangji University, Wonju 26339, South Korea; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2405844022025208Molecular dynamics simulationPrincipal component analysisEAEMultiple sclerosisGrancalcinGROMACS
spellingShingle Shamrat Kumar Paul
Md. Saddam
Khandoker Asiqur Rahaman
Jong-Gu Choi
Sang-Suk Lee
Mahbub Hasan
Molecular modeling, molecular dynamics simulation, and essential dynamics analysis of grancalcin: An upregulated biomarker in experimental autoimmune encephalomyelitis mice
Heliyon
Molecular dynamics simulation
Principal component analysis
EAE
Multiple sclerosis
Grancalcin
GROMACS
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 Molecular dynamics simulation
Principal component analysis
EAE
Multiple sclerosis
Grancalcin
GROMACS
url http://www.sciencedirect.com/science/article/pii/S2405844022025208
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