Abstract
BACKGROUND: Microplastics are tiny plastic particles, typically less than 5 mm in size, formed from the breakdown of larger plastic products. This breakdown releases additives, including benzyl butyl phthalate (BBP), into the environment. Humans can be exposed to BBP through contaminated food and water, inhalation, and dermal contact. AIM: Research suggests that BBP, like other phthalates, may have neurotoxic effects, potentially contributing to neurodevelopmental disorders, though its specific toxic targets are not yet clear. METHODOLOGY: In this study, high-performance computational methods were used to identify potential neurotoxic targets of BBP. The findings indicate that BBP has a strong potential to interact with Parkin (PRKN) and Pyruvate dehydrogenase lipoamide kinase isozyme 1 (PDK1), with binding scores of -5.35 kcal/mol, -5.56 kcal/mol, respectively. The PRKN and PDK1 BBP complexes were stable throughout the simulation period, as evidenced by the system's backbone exhibiting slight fluctuations and binding energies confirmed by molecular dynamics (MD) simulation trajectories. RESULTS: The MMPBSA analysis revealed free binding energies of -21.29 kcal/mol and - 27.06 kcal/mol for the PRKN and PDK1 BBP complexes, respectively. The interaction energies of BBP with PRKN and PDK1 were also within an acceptable range, at -113.68 ± 3.1 kJ/mol and - 117.54 ± 6.2 kJ/mol, respectively. Additionally, density-functional theory (DFT) based optimization showed negative values for the highest occupied molecular orbital (HOMO) -6.934 eV and lowest unoccupied molecular orbital (LUMO) -1.562 eV, indicating that BBP is energetically stable, which is crucial for forming a stable ligand-protein complex. CONCLUSION: Overall, the computational investigation reveals that BBP has the potential to interact with PRKN and PDK1, leading to neurodegeneration.