Comparative Binding Analysis by Computational Methods and Quartz Crystal Microbalance: Case of hnRNPA2B1 Protein and Irinotecan Drug

Irinotecan (IRT) is a well-established anticancer drug that primarily targets topoisomerase 1. This study reveals a direct interaction between IRT and heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1), which is a protein implicated in the progression of different kinds of cancers. The Quartz Crystal Microbalance (QCM) was applied to measure a binding affinity between IRT and hnRNPA2B1, resulting in an apparent binding constant <i>K</i>_{D_QCM} of (15 ± 1) × 10^-3, which is comparable to the apparent binding constant <i>K</i>_{D_QCM} of (17 ± 2) × 10^-3 for the reference ligand camptothecin. Further computational analysis via molecular docking and molecular dynamics (MD) simulations demonstrated stable binding of IRT to the RNA recognition domain (RRM) of hnRNPA2B1, yielding a binding free energy Δ<i>G</i> of -10.36 kcal·mol^-1. These findings suggest that IRT may exert an inhibitory effect on hnRNPA2B1, potentially contributing to its anticancer activity beyond topoisomerase 1 inhibition.