| Abstrakt: |
Rosacea is a skin condition characterized by inflammation, and efforts to develop its treatment are ongoing. Overactivation of the enzymes Kallikrein-5 (KLK5) and peptide Cathelicidin (LL-37) has been identified as a regulatory factor in rosacea. Excessive activation of KLK5 and LL-37 can lead to chronic inflammation and manifest in symptoms like facial redness, swelling, and the formation of pustules. These molecules are crucial in the inflammatory process and can compromise the skin's integrity. Our study aimed to identify potential compounds from the ZINC20 database for rosacea therapy using virtual screening guided by in-silico molecular docking studies, insilico molecular dynamics simulations, and in-silico protein-peptide molecular docking studies targeting KLK5 and LL-37. Initially, we optimized the geometries of selected compounds from the ZINC20 database and then performed molecular docking studies and molecular dynamics simulations on KLK5, as well as protein-peptide molecular docking studies on LL-37. During drug similarity analysis of the compounds, we observed no violations of Lipinski's five rules and found no evidence of hepatotoxicity. Based on the docking score for KLK5, we identified ZINC compounds with favorable molecular interactions. Subsequently, we conducted 200 ns MD simulations and assessed system stability using RMSD, RMSF, Rg, H-bonding, RDF, SASA, and MM-PBSA. Among the ZINC compounds, ZINC000022339916 demonstrated superior stability compared to others, as well as azelaic acid and native ligands. Moreover, ZINC000888090135 and ZINC000888088617 were capable of preventing LL-37 from binding to the surface of KLK5. These findings highlight the potential of these compounds in inhibiting KLK5 activity and disrupting LL-37 interactions in the context of rosacea treatment. [ABSTRACT FROM AUTHOR] |
