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Effect of non-synonymous single nucleotide polymorphisms in rho domain of TAGAP: structural modeling and molecular dynamics simulation approach
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| Author:
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SHRI PREETHI M, NIKITA JAIN, YACHANA CHAKRAVARTY, ASHA DEVI S
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| Abstract:
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Background: Non-synonymous Single Nucleotide Polymorphisms (ns SNPs) in individuals make them susceptible to several disease conditions. One such case is that ns SNPs in T-cell activation Rho GTPase activating protein expressed by TAGAP gene in activated T cells is reported to be associated with rheumatoid arthritis, celiac disease, multiple sclerosis, Crohn's disease.
Objective: The research was done Insilco, where computational tools were used to identify the non-synonymous SNPs in the TAGAP gene followed by modeling of the identified SNPs which is more deleterious to the TAGAP protein structure and stability using Swiss Model and to validate the structure.
Methods: In order to identify nsSNPs that might be deleterious to the structural stability of TAGAP protein, we have employed computational tools such as I mutant 2.0, PolyPhen-2, PROVEAN, and PANTHER. This was followed by homology modeling using the Swiss Model for the predicted and identified nsSNPs deleterious to the stability and structure of the protein and for its native structure. Further, the modeled structures were validated by performing Molecular dynamics simulation using the GROMACS package.
Results: We observed two mutants, rs759674898 (Pro103Leu) and rs773039880 (Ser220Gly) showed significant scores in all the four tools employed, additionally homology modeling with Swiss model showed Native, Pro103Leu and Ser220Gly protein structures were found to be 42.78%, 42.27% and 42.27% identical respectively to the template protein and validated for its stability by performing Molecular Dynamics simulation using GROMACs package.
Conclusion: This indifference in structure of mutated proteins (Pro103Leu, Ser220Gly) compared to the structure of native protein may have an effect on the function of the protein as it lies in the Rho domain of TAGAP gene. This might be considered as a therapeutic target in association with several diseases.
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| Keyword:
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TAGAP; non-synonymous SNP; homology modeling; molecular dynamics
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| EOI:
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-
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| DOI:
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https://doi.org/10.31838/ijpr/2020.SP1.329
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| Download:
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