In Silico Approach in the Evaluation of Pro-Inflammatory Potential of Polycyclic Aromatic Hydrocarbons and Volatile Organic Compounds through Binding Affinity to the Human Toll-Like Receptor 4.

Polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs) are widespread across the globe, existing in the environment in complex mixtures potentially capable of initiating respiratory illnesses. Here, we use an in silico approach to evaluate the potential pro-inflammatory effects of various carcinogenic PAHs and VOCs through their binding affinity towards the human toll-like receptor 4 (TLR4). For receptors and ligands, RCSB Protein Data Bank and PubChem were used in obtaining their 3D structures, respectively. Autodock Vina was utilized to obtain the best docking poses and binding affinities of each PAH and VOC. Out of the 14 PAHs included in this study, indeno(1,2,3-cd)pyrene, benzo(ghi)perylene, and benzo[a]pyrene had the highest binding affinity values of -10, -9, and -8.9 kcal/mol, respectively. For the VOCs, out of the 10 compounds studied, benzene, 1,4-dichlorobenzene, and styrene had the highest binding affinity values of -3.6, -3.9, and -4.6 kcal/mol, respectively. Compounds with higher affinity than LPS (-4.1 kcal/com) could potentially induce inflammation, while compounds with lower affinity would be less likely to induce an inflammatory response. Meanwhile, molecular dynamics simulation and RMSF statistical analysis proved that the protein, TLR4, stably preserve its conformation despite ligand interactions. Overall, the structure of the TLR4 was considered inflexible.