The effects of an external electric field on the binding affinity for protein-ligand complexes was determined by applying electric field E(ext) to a water cluster containing two electric dipoles separated by a certain distance. The mean forces on these two dipoles were computed from the trajectories of molecular dynamics simulations. The results showed that the mean attractive force and the binding affinity between these two dipoles decreased with increasing E(ext). Two factors governing the effects of E(ext) on the binding affinity of protein-ligand interactions were proposed. (1) When E(ext) is applied to a water cluster containing protein-ligand complexes, the water molecules neighboring ligand will be repelled from the ligand; the mean van der Waals repulsive force exerted on the ligand by these water molecules would decrease, leading to a decrease in the binding affinity between the protein and the ligand. (2) The mean electrostatic force exerted on the ligand by the water molecules polarized by E(ext) is thought to result from the dielectric polarization (P(protein)) in the region occupied by the protein, where P(protein) is proportional to -E(ext).