We present results of the investigation of the cavity creation/annihilation effect in view of formation of the protein-ligand (PL) complexes. The protein and ligand were considered as rigid structures. The change of the cavity creation/annihilation free energy Delta G(cav) was calculated for three PL complexes using the thermodynamic integration procedure with the original algorithm for growing the interaction potential between the cavity and the water molecules. The thermodynamic cycle consists of two stages, annihilation of the cavity of the ligand for the unbound state and its creation at the active site of the protein (bound state). It was revealed that for all complexes under investigation, the values of Delta G(cav) are negative and favorable for binding. The main contribution to Delta G(cav) appears due to the annihilation of the cavity of the ligand. All computations were made using the parallel version of CAVE code, elaborated in our preceding work.