Evaluation of the ABCG2 Charge Model in Protein-Ligand Binding Free-Energy Calculations.

Accurate binding free energy prediction is vital for drug design, motivating the assessment of new force field models. Here, we evaluate the ABCG2 charge model with nonequilibrium alchemical free-energy simulations. GAFF2/ABCG2 achieves higher hydration free energy accuracy but does not outperform GAFF2/AM1-BCC for protein-ligand binding free energy. Both charge models exhibit comparable accuracy and compound ranking across targets, indicating that property-specific force field optimization does not guarantee improved related-property performance.