Computational methods for examining the binding of organic ligands to target proteins play a crucial role in structure-based drug design. While designing organic ligands that can potentially become drug molecules, a ligand's selectivity and binding free energy upon its binding to the target protein are optimized. Upon ligand binding, water molecules and ions that were previously occupying the protein's binding site are displaced from the binding site and are released to the solvent. The entropic contribution of the release of the water molecules to the solvent is a principal component in the binding free energy of the proteinligand complex.