hnRNP A2B1 as a promising therapeutic target for radiomodulatory drug development: evidence from computational and experimental studies

Radiation modulation is critical due to the growing risks of radiation exposure in medical, occupational, and environmental settings. This study explored the potential of heterogeneous nuclear ribonucleoproteins (hnRNPs), particularly hnRNP A2B1, as therapeutic targets for radiomodulatory drugs. <i>In vitro</i> experiments on human endothelial cells exposed to various X-ray doses revealed a dose-dependent increase in hnRNP A2B1 expression, with the histochemical score increasing significantly from 105 to 280 at 8.0 Gy. Using in silico molecular docking, 33 radiomodulatory agents were evaluated for their binding affinities with hnRNP A2B1. Notable ligands, such as hesperidin and psoralidin, demonstrated strong binding affinities (ΔG_tot values: -17.2 and -17.9 kcal⋅mol^-1, respectively). Finally, molecular dynamics simulations confirmed that psoralidin had the highest affinity for hnRNP A2B1 using implicit solvation models. Overall, this study revealed that hnRNP A2B1 is vital for cellular radiomodulation and is a promising target for radiomodulatory drugs that could have radioprotective or radiosensitizing effects.