Decoding DNA Interactions of Cosmetic Compounds: A Multi-Scale In-Silico Approach

The growing presence of chemical substances in cosmetics has raised concerns about their genotoxicity and potential interactions with DNA. In this study, an in silico strategy comprising molecular docking, interaction analysis, ADME and toxicity prediction, and molecular dynamics (MD) simulation was used to analyze the DNA-binding capacity of 130 common cosmetic chemicals using B-DNA (ID: 1BNA). According to the findings, many molecules showed strong binding affinities for the target sequence in docking simulations with AutoDock 4.2.6, including Clobetasol propionate (ΔG = -12.9 kcal/mol), Clobetasol, Imidurea, and Hyperoside. Groove binding and hydrogen bonding were the most important contributors to DNA-ligand binding, according to the PLIP interaction profile. SwissADME and ProTox 3.0 were used to assess ADMET properties and toxicity. Based on binding affinity, interaction mode, and toxicity levels, three chemicals, including Clobetasol propionate, Clobetasol, and Benzophenone-2, were selected for MD simulation. It was found that among these three molecules, Clobetasol propionate forms the best DNA-ligand complex, while Clobetasol causes local conformational changes, and weak DNA interaction was observed with Benzophenone-2. Overall, this hierarchical computational analysis indicates that Clobetasol propionate and Clobetasol are strong DNA binders, which could have potential genotoxic implications, whereas Benzophenone-2 caused moderate destabilization. The in silico method successfully identified and ranked cosmetic ingredients with strong DNA-binding potential, providing insights into their genotoxicity. This aids future lab tests for safety.