Trypsin-ligand binding free energy calculation with AMOEBA

The binding free energies of several benzamidine -like inhibitors to trypsin were examined using a polarizable molecular mechanics potential. All the computed binding free energies are in good agreement with the experimental data. From free energy decomposition, electrostatic interaction was indicated to be the driving force for the binding. MD simulations show that the ligands form hydrogen bonds with trypsin and water molecules nearby in a competitive fashion. While the binding free energy is independent of the ligand dipole moment, it shows a strong correlation with the ligand molecular polarizability.

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