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Structural and Functional Impact of Damaging Nonsynonymous Single Nucleotide Polymorphisms (nsSNPs) on Human VPS35 Protein Using Computational Approaches
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DOI：10.1109/TCBB.2021.3118054.png)
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Abstract
En 中文
Parkinson's disease is the second most common progressive neurodegenerative movement disorder. Mutations in retromer complex subunit and VPS35 represent the secondmost common cause of late-onset familial Parkinson's disease. The mutation in VPS35 can disrupt the normal protein functions resulting in Parkinson's disease. The aimof this study was the identification of deleterious missense Single Nucleotide Polymorphisms (nsSNPs) and their structural and functional impact on the VPS35 protein. In this study, several insilico toolswere used to identify deleterious and disease-associated nsSNPs. 3D structure of VPS35 proteinwas constructed throughMODELLER 9.2, normalized using FOLDX, and evaluated through RAMPAGE and ERRATwhereas, FOLDX was used for mutagenesis. 25 ligandswere obtained from literature and docked using PyRx 0.8 software. Based on the binding affinity, five ligands i.e., PG4, MSE, GOL, EDO, and CAF were further analyzed. Molecular Dynamic simulation analysiswas performed usingGROMACS 5.1.4, where temperature, pressure, density, RMSD, RMSF, Rg, and SASA graphswere analyzed. The results showed that the mutations Y67H, R524W, and D620N had a structural and functional impact on the VPS35 protein. The current findings will help in appropriate drug design against the disease caused by these mutations in a large population using in-vitro study.
Keywords:
Proteins
Diseases
Biological system modeling
Amino acids
Sorting
Bioinformatics
Tools
Parkinson disease
VPS35
protein modeling
molecular dynamic simulation
drug designing
mutations
Journal
I
IF:
3.4
Papers:
3.3K
Citations:
6.4K
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