Binding free energy calculations of adenosine deaminase inhibitors

The interactions between four inhibitors and adenosine deaminase (ADA) were examined by calculating their binding
free energies after molecular dynamics simulations. A bonded model was used to represent the electrostatic potentials of the zinc
coordination site. The charge distribution of the model was derived by using a two-stage electrostatic potential fitting calculations.
The calculated binding free energies are in good agreement with the experimental data and the ranking of binding affinities is well
reproduced. Notably, our findings suggest that non-polar contributions play an important role for ADA–inhibitor interactions.