Exploring natural compounds and siRNA-based therapeutics for targeted acne vulgaris: A computational and bioinformatic approach

Acne vulgaris is a multifactorial dermatological condition that affects millions of people worldwide. This study investigates the potential of natural compounds and siRNA molecules as novel therapeutic agents in acne vulgaris. Five ligands, guar gum, polyvinyl alcohol (PVA), curcumin, chitosan, and benzoyl peroxide (BPO), were evaluated for their drug-like properties using computational tools. The JNK1, KAS III, and exo-β-1,4-mannosidase are key proteins involved in acne pathogenesis and are targeted in the present study. Docking analysis was performed to reveal the strong binding affinities of curcumin and benzoyl peroxide to JNK1. The ADMET analysis further validated the anti-acne potential of these compounds for further clinical trials. The molecular dynamics (MD) simulation provided valuable insights into the stability and flexibility of the complexes. The docking analysis revealed strong binding affinities of curcumin and benzoyl peroxide to JNK1, with binding energies of −8.1 kcal/mol and −7.4 kcal/mol, respectively, and to exo-β-1,4-mannosidase with binding energies of −8.0 kcal/mol and −7.8 kcal/mol, respectively. The molecular dynamics (MD) simulation provided valuable insights into the stability, flexibility, and conformational behavior of the curcumin/JNK1 and siRNA G1/6GVB complexes. The root-mean-square deviation (RMSD) analysis indicated that the curcumin/JNK1 complex stabilized rapidly within 10 ns of the initial phase and maintained an RMSD of 0.15–0.18 nm, suggesting strong structural integrity. In contrast, the siRNA G1/6GVB complex exhibited increased flexibility, with RMSD values fluctuating between 0.6 and 0.8 nm, as expected given the inherent dynamic nature of RNA molecules. The root mean square fluctuation (RMSF) further confirmed these findings, as most residues in the curcumin–JNK1 complex remained stable (< 0.15 nm), and only terminal regions showed fluctuations (0.35–0.40 nm). Meanwhile, the siRNA G1/6GVB complex showed greater flexibility, with RMSF peaks of 0.5–0.7 nm, particularly in loops and surface-exposed regions. These findings suggest that the top-scoring natural compound and siRNA molecule present a promising alternative treatment for acne vulgaris, warranting further research to confirm their efficacy and safety in clinical settings.