Computational Discovery of an Allosteric Pocket on APOBEC3B and the Impact of Metal Contamination on Inhibitor Validation

Computational screening identified a novel allosteric pocket on APOBEC3B with 13 candidate inhibitors, advancing potential tumor therapy options.

• Why it matters: APOBEC3B contributes to tumor mutations and resistance, making it a critical target for cancer treatment; however, effective inhibitors are lacking and require discovery.
• What they did: Using molecular dynamics simulations and solvent mapping, researchers virtually screened approximately 110,000 compounds against APOBEC3B’s allosteric and active sites, then validated 13 hits through biochemical and NMR assays.
• The result: The identified compounds selectively bind to APOBEC3B over APOBEC3A, with MD simulations suggesting steric differences underpin this selectivity, enabling further development of targeted inhibitors.