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 KD_QCM of (15 ±
1) × 10–3, which is comparable to the apparent
binding constant KD_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 ΔG 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.