Accurate calculation of the binding free energies between a protein and a ligand is the primary objective of structure-based drug design, but it still remains a challenging problem. In this work, we apply the screening molecular mechanics/Poisson Boltzmann surface area (MM/PBSA) method to calculate the binding affinity of protein-ligand interactions. Our results show that the performance of the screening MM/PBSA is better than that of the standard MM/PBSA, especially in a charged-ligand system. In addition, we also investigate the effect of the solute dielectric constant on the results, and find that the optimal solute dielectric constants are different between the neutral-ligand system and the charged-ligand system. Moreover, we also evaluate the effect of the atomic-charge methods on the performance of the screening MM/PBSA. The present study demonstrates that the screening MM/PBSA should be a reliable method for calculating binding energy of biosystems.