The structural, dynamical, and functional importance of water molecules for biomolecular structure and recognition is well-known. Water contributes significantly to the stability of biomacromolecules and plays a crucial role in molecular association. In general, buried water molecule is believed to be involved in local structural stabilization in proteins and DNA. These water molecules are critical for the binding affinity or specificity of protein-ligand complexes. It is important in the design of new ligands. X-ray crystallography, NMR spectroscopy, and neutron diffraction are typical experimental methods to analyze presence of water molecules at atomic level. However, high-resolution structures (better than 1.5 A) are preferred for reliable analysis of structural aspects of water molecules associated with host protein. In absence of high-resolution experimental data, theoretical studies, such as molecular dynamics simulations, represent complementary methods to locate water positions and understand the dynamics and energetics of these water molecules. Water molecules behavior based on results on molecular dynamics simulations of enzyme cyclin-dependent kinase cdk2 and its complexes with natural substrate (ATP) and two inhibitors (roscovitine, isopentenyladenine) will be discussed. Enzyme cyclin-dependent kinase cdk2 plays an important role in cell cycle. The inhibitors of this enzyme are potential anticancer therapeutics. The results of our study show the substrate dependent and independent positions in cdk2 that can be solvated. The interaction energy of these water molecules with protein and with substrate will be discussed. The results will be compared with X-ray crystallography data.