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

## TL;DR

This study shows that hnRNP A2B1 is a key protein involved in radiation response and could be a target for drugs to protect or sensitize cells to radiation.

## Contribution

The study identifies hnRNP A2B1 as a novel therapeutic target for radiomodulatory drugs using both computational and experimental approaches.

## Key findings

- hnRNP A2B1 expression in endothelial cells increases with higher X-ray doses.
- Hesperidin and psoralidin showed strong binding affinities to hnRNP A2B1.
- Molecular dynamics simulations confirmed psoralidin's high affinity for hnRNP A2B1.

## Abstract

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. In vitro 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 (ΔGtot 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.

Diagram illustrating the process involving mAb HNRNPA2B1, endothelial cells, and X-ray exposure. mAb HNRNPA2B1 is depicted targeting the HNRNPA2B1 protein. Endothelial cells respond to X-ray exposure. The protein-ligand complex is highlighted, indicating radio protection on the left and radio sensitization on the right.