• Syeda Marium Ali

• Khalida Naveed

• Syed Noman Ali

• Syeda Hira Seemab

• Mahwish Saleem

• Ayesha Majid

تلخیص

Toll like receptor is involved in detecting pathogen-associated molecular patterns of various pathogens and trigger an immune response against microbial infection. SNPs effect on structure and function of TLR3 gene was carried out using computational analysis during the current study. The 340 non synonymous Single nucleotide polymorphisms (nsSNPs) were evaluated either effecting function of TLR3 or using seven different tools employing specific threshold values. A total of four nsSNPs (L159F, L545P, N284I, and P880Q) were found to have deleterious effects on the TLR3 protein function and were therefore selected for further analysis. All of the variants showed increased free energy, although L159F exhibited the highest energy increase while the RMSD (root-mean-square deviation) values of L159F and L545P are greater than 0.15 strongly indicated structural changes. By using various publicly available computational tools, 5 deleterious mutations (L159F, L545P, N284I, L412F and P880Q) in the coding region of the TLR3 gene were identified. Structurally, the selected mutants (especially L159F, L545P and N284I) were predicted to be significant for pathogenicity. Among the 06 potential nsSNPs, the L159F, L545P and N284I mutants were found to cause decreased aggregation of the TLR3 protein. Therefore, these nsSNPs should be considered as important candidates in causing diseases related to TLR3 gene malfunction.

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