Exploring the interaction between 3-D structure of TLR 9 and prostaglandin analogues

Abstract

Toll-like receptor 9 (TLR9) is a class of pattern recognition receptors (PRRs) approved to have an essential role with the development of autoimmune illnesses such as psoriasis and arthritis. TRL9 is predominantly expressed on dendritic cells (DCs) and macrophages, and it mediates antigen presentation to T cells. In this regard, interfering with this interaction by inhibiting TLR9 could be an effective immunotherapy strategy for certain diseases. Based on previous research (Degraaf et al.2014, Farrugia et al., 2017) indicating that prostaglandins play a significant role in regulating or reducing the expression of TLRs, their function against intracellular TLRs such as TLR9 may involve direct inhibition of these receptors. The 3D structure of the human-TLR9 is modelled and described molecularly and then prepared to be docked by prostaglandin analogues, followed by molecular dynamic (MD) simulation, MM/PBSA analysis, and PCA analysis. The study uncovered significant direct interactions between TLR9 and prostaglandin analogues, specifically with the FDA-approved Bimatoprost (BI), which demonstrates the highest binding affinity (calculated as an estimated affinity) and an interesting MM/PBSA score and should be the primary focus of future research into the treatment of autoimmune diseases. In addition, the modelled structure of human-TLR9 and its binding site described in this study could serve as a useful starting point for the development of additional inhibitors