Targeting OGG1 for Pulmonary Fibrosis: An Integrated In Silico Study with Quantum Chemical Calculations, Docking, Pharmacophore Modeling, Molecular Dynamics, and ADMET Evaluation

Abstract 8‐oxoguanine DNA glycosylase 1 (OGG1) regulates oxidative stress and promotes fibrosis through TGF‐β and NF‐κB pathways. Its inhibition holds therapeutic potential, making it a promising target for pulmonary fibrosis treatment. In this study, a diverse collection of natural products with reported antifibrotic activity was evaluated using integrated molecular modeling approaches to identify potential OGG1 inhibitors. Molecular docking and molecular dynamics simulations revealed stable and favorable interactions between several compounds and the OGG1 active site, suggesting strong inhibitory potential. A pharmacophore model was developed to capture key features responsible for OGG1 inhibition, guiding the identification of promising candidates such as curcumin, rosmarinic acid, quercetin, shikonin, and scutellarein. Further computational analyses, including DFT analysis, drug‐likeness screening, and ADME/Tox evaluation, indicated that several natural compounds exhibit superior reactivity, pharmacokinetic properties, and safety profiles compared to known antifibrotic agents. These findings highlight a subset of natural products as potential OGG1‐targeting antifibrotic leads, providing a foundation for future experimental validation and drug development.