Bioinformatic Analysis of Human TLR4 Coding Variations Associated with Ocular Infection: A Structural Prediction and Molecular Docking Studies

In 2023, Pakistan faced a widespread outbreak of conjunctivitis, affecting nearly 400,000 individuals. The rapid transmission was driven by environmental factors, infectious agents, and allergens, with common symptoms including eye redness, swelling, tearing, and discharge. In response, a pioneering bioinformatics study examined the TLR4 gene variants, given TLR4 role in immune response, although direct genetic links to conjunctivitis are not yet established. Using Swiss Model and SAVESV6.1, a 3D model of TLR4 was developed, verified with a QMEAN-Z score of -0.81 and a ProSA score of -7.51, affirming its reliability. This study identified 82 highly deleterious nsSNPs through multiple computational tools, with 12 significantly harmful variants N44H, S207C, N185S, and D84A exhibiting notable structural impacts. Docking studies with both wild-type and mutant forms of TLR4 tested 17 compounds, revealing Apigenin, GN8, SYUIQ-5, S-adenosylmethionine, Vixotrigine, and Tetracycline as potential inhibitors due to their strong affinities for TLR4. These findings suggest that these compounds may offer therapeutic potential for conjunctivitis, though further experimental validation is needed.