Robust anti-inflammatory activity of genistein against neutrophil elastase: a microsecond molecular dynamics simulation study

Human Neutrophil Elastase (HNE) is one of the major causes of tissue destruction in numerous chronic and inflammatory disorders and has been reported as a therapeutic target for inflammatory diseases. Overexpression of this enzyme plays a critical role in the pathogenesis of rheumatoid arthritis (RA). The focus of this study is to identify potent natural inhibitors that could target the active site of the HNE through the use of computational methods. The molecular structure of small molecules was retrieved from several natural compound databases. This was followed by structure-based virtual screening, molecular docking, ADMET property predictions and molecular dynamic simulation studies to screen potential HNE inhibitors. In total, 1881 natural compounds were extracted and subjected to molecular docking studies, and 10 compounds were found to have good interactions, exhibiting the best docking scores. Genistein showed higher binding efficacy (-10.28 Kcal/mol) to HNE in comparison to other natural compounds. The conformational stability of the docked complex of the ELANE gene (HNE) with genistein was assessed using 1-microsecond molecular dynamic simulation (MDs), which reliably revealed the unique stereochemical alteration of the complex, indicating its conformational stability and flexibility. Alterations in the enzyme structure upon complex formation were further characterized through clustering analysis and linear interaction energy (LIE) calculation. The outcomes of this research propose novel potential candidates against target HNE. Communicated by Ramaswamy H. Sarma