Comprehensive analysis of non-synonymous SNPs related to Parkinson’s disease and molecular dynamics simulation of PRKN mutants
Parkinson’s disease (PD) is associated with a mutation in the PRKN (Parkin RBR E3 Ubiquitin Protein Ligase). PRKN functions as maintaining dopamine (DA) neuronal homeostasis and homeostasis dysfunction, which play an important role in early PD onset. The main objective behind this work is to identif...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Results in Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211715623000565 |
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| author | Sapna Pandey Neha Maurya Himanshu Avashthi Pramod Katara Satendra Singh Budhayash Gautam Dev Bukhsh Singh |
| author_facet | Sapna Pandey Neha Maurya Himanshu Avashthi Pramod Katara Satendra Singh Budhayash Gautam Dev Bukhsh Singh |
| author_sort | Sapna Pandey |
| collection | DOAJ |
| description | Parkinson’s disease (PD) is associated with a mutation in the PRKN (Parkin RBR E3 Ubiquitin Protein Ligase). PRKN functions as maintaining dopamine (DA) neuronal homeostasis and homeostasis dysfunction, which play an important role in early PD onset. The main objective behind this work is to identify PRKN deleterious single nucleotide polymorphism (SNPs) by computational analysis and implement molecular dynamic simulation (MDS) to study the structural and functional properties of native and mutant proteins. We found A46T, I23T, C212Y, D243N, E28G, G359D, P37L, Q34R, R256C, R275W, R366W, and R402C as the most delirious and disease-linked by using different bioinformatics tools such as ANNOVAR (SIFT & POLYPHEN2) annotation, SNPs & GO, PROVEAN, and I-Mutant3.0. To understand protein functionality and atomic arrangement in 3-D space, the comparative modeling of native and mutant PRKN protein (A46T, I23T, C212Y, D243N, E28G, G359D, P37L, Q34R, R256C, R275W, R366W, and R402C) was performed with standalone MODELLER 9.15 program. Finally, MDS analysis was done by using the GROMACS 5.1.5 comprehensive package to study the structural stability and dynamic perturbations in native and mutant PRKN proteins. MDS analysis shows more flexibility in native structures in comparison to mutant structures. Mutant structures show structural perturbation and result in loss of PRKN protein function. The findings of this study might assist wet-lab studies to create effective pharmacological treatments against PD targeting PRKN. |
| first_indexed | 2024-03-13T04:13:18Z |
| format | Article |
| id | doaj.art-2eb2b74f5387403db4f4bc3ca22f6f97 |
| institution | Directory Open Access Journal |
| issn | 2211-7156 |
| language | English |
| last_indexed | 2024-03-13T04:13:18Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Results in Chemistry |
| spelling | doaj.art-2eb2b74f5387403db4f4bc3ca22f6f972023-06-21T06:52:08ZengElsevierResults in Chemistry2211-71562023-01-015100817Comprehensive analysis of non-synonymous SNPs related to Parkinson’s disease and molecular dynamics simulation of PRKN mutantsSapna Pandey0Neha Maurya1Himanshu Avashthi2Pramod Katara3Satendra Singh4Budhayash Gautam5Dev Bukhsh Singh6Department of Computational Biology & Bioinformatics, Jacob Institute of Biotechnology & Bio-Engineering, Sam Higginbottom University of Agriculture, Technology and Science (SHUATS), Prayagraj, IndiaDepartment of Biotechnology, Motilal Nehru National Institute of Technology (MNNIT), Prayagraj, IndiaDivision of Agricultural Bioinformatics, ICAR-Indian Agricultural Statistics Research Institute, New Delhi 110012, IndiaCentre of Bioinformatics, University of Allahabad, Prayagraj, IndiaDepartment of Computational Biology & Bioinformatics, Jacob Institute of Biotechnology & Bio-Engineering, Sam Higginbottom University of Agriculture, Technology and Science (SHUATS), Prayagraj, IndiaDepartment of Computational Biology & Bioinformatics, Jacob Institute of Biotechnology & Bio-Engineering, Sam Higginbottom University of Agriculture, Technology and Science (SHUATS), Prayagraj, India; Corresponding authors.Department of Biotechnology, Siddharth University, Kapilvastu, Siddharth Nagar, 272202, India; Corresponding authors.Parkinson’s disease (PD) is associated with a mutation in the PRKN (Parkin RBR E3 Ubiquitin Protein Ligase). PRKN functions as maintaining dopamine (DA) neuronal homeostasis and homeostasis dysfunction, which play an important role in early PD onset. The main objective behind this work is to identify PRKN deleterious single nucleotide polymorphism (SNPs) by computational analysis and implement molecular dynamic simulation (MDS) to study the structural and functional properties of native and mutant proteins. We found A46T, I23T, C212Y, D243N, E28G, G359D, P37L, Q34R, R256C, R275W, R366W, and R402C as the most delirious and disease-linked by using different bioinformatics tools such as ANNOVAR (SIFT & POLYPHEN2) annotation, SNPs & GO, PROVEAN, and I-Mutant3.0. To understand protein functionality and atomic arrangement in 3-D space, the comparative modeling of native and mutant PRKN protein (A46T, I23T, C212Y, D243N, E28G, G359D, P37L, Q34R, R256C, R275W, R366W, and R402C) was performed with standalone MODELLER 9.15 program. Finally, MDS analysis was done by using the GROMACS 5.1.5 comprehensive package to study the structural stability and dynamic perturbations in native and mutant PRKN proteins. MDS analysis shows more flexibility in native structures in comparison to mutant structures. Mutant structures show structural perturbation and result in loss of PRKN protein function. The findings of this study might assist wet-lab studies to create effective pharmacological treatments against PD targeting PRKN.http://www.sciencedirect.com/science/article/pii/S2211715623000565Parkinson’s Disease PRKNNon-synonymous SNPsMolecular dynamic simulationAnnovarMutation |
| spellingShingle | Sapna Pandey Neha Maurya Himanshu Avashthi Pramod Katara Satendra Singh Budhayash Gautam Dev Bukhsh Singh Comprehensive analysis of non-synonymous SNPs related to Parkinson’s disease and molecular dynamics simulation of PRKN mutants Results in Chemistry Parkinson’s Disease PRKN Non-synonymous SNPs Molecular dynamic simulation Annovar Mutation |
| title | Comprehensive analysis of non-synonymous SNPs related to Parkinson’s disease and molecular dynamics simulation of PRKN mutants |
| title_full | Comprehensive analysis of non-synonymous SNPs related to Parkinson’s disease and molecular dynamics simulation of PRKN mutants |
| title_fullStr | Comprehensive analysis of non-synonymous SNPs related to Parkinson’s disease and molecular dynamics simulation of PRKN mutants |
| title_full_unstemmed | Comprehensive analysis of non-synonymous SNPs related to Parkinson’s disease and molecular dynamics simulation of PRKN mutants |
| title_short | Comprehensive analysis of non-synonymous SNPs related to Parkinson’s disease and molecular dynamics simulation of PRKN mutants |
| title_sort | comprehensive analysis of non synonymous snps related to parkinson s disease and molecular dynamics simulation of prkn mutants |
| topic | Parkinson’s Disease PRKN Non-synonymous SNPs Molecular dynamic simulation Annovar Mutation |
| url | http://www.sciencedirect.com/science/article/pii/S2211715623000565 |
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