Computational Estimation of Compounds Isolated from Asarum geophilum as Potential Inhibitors of Janus Kinase 2 (JAK2) Protein

Asarum geophilum is a narrowly distributed species in Vietnam with significant untapped bioactive potential. Numerous compounds, predominantly flavonoids have been isolated from Asarum species. This study aimed to screen and evaluate the inhibitory potential of flavonoid compounds (1 – 18) isolated from Asarum geophilum against the JAK2 protein using computational models. The interaction of the isolated compounds with JAK2 protein was investigated in silico via molecular docking, and molecular dynamics simulations. The molecular docking study successfully positioned eighteen isolated compounds from Asarum geophilum within the Janus kinase 2 (JAK2) protein active site. The isolated compounds demonstrated binding affinities ranging from -6.630 to -9.521 kcal/mol (mean: -8.209 kcal/mol). Nine top-performing ligands (compounds 7, 8, 9, 11, 12, 13, 14, 16, and 18) with ΔGdock < -8.0 kcal/mol were selected for further analysis. Conformational studies revealed these lead compounds formed stable interactions with key JAK2 amino acid residues. Notably, compound 14 exhibited exceptional binding characteristics (ΔGLIE = -21.78 kcal/mol), with dissociation metrics significantly outperforming both other screened compounds and established JAK2 inhibitors. The ΔGLIE values for all leads (-8.35 to -21.78 kcal/mol) substantially exceeded those of reference inhibitors, suggesting superior target engagement potential.