In Silico Toxicity Assessment of Organophosphates: A DFT and Molecular Docking Study on Their Interaction with Human Serum Albumin (HSA)

This study presents an _in silico_ analysis of the toxicity of Organophosphates (OPs) through their interaction with Human Serum Albumin (HSA) protein using density functional theory (DFT) and molecular docking approaches. Organophosphates, known for their widespread use as pesticides, have raised significant concerns due to their potential toxicological effects. To investigate the molecular mechanisms underlying OP toxicity, we conducted DFT calculations to determine the electronic properties and reactivity of selective OP compounds. Molecular docking simulations were performed to explore the binding affinity, interaction sites, and conformational changes of HSA upon exposure to OPs. The DFT analysis revealed key electronic descriptors, such as HOMO-LUMO gap and electrostatic potential, that indicate high reactivity of OPs with biological molecules. Docking results showed strong binding affinities between OPs and HSA, particularly at sites involved in metabolite and drug transport, suggesting potential interference with the protein’s native function. The interaction of OPs with HSA was further supported by molecular dynamics simulations, which confirmed the stability of the OP-HSA complex over time. These findings provide critical insights into the molecular basis of organophosphate toxicity, emphasizing the importance of their interaction with HSA. The combined DFT and molecular docking approach offers a valuable framework for predicting the toxicological behavior of OPs and lays the foundation for further _in vitro_ and _in vivo_ studies.