Figure 5.
A typical thermodynamic cycle for the calculation of absolute binding free energy of host and ligand in Tinker. The completely solvated ligand and a solvent box are associated through intermediate states with gradual changes in the order parameters of vdW and electrostatics. While the order parameter of electrostatics affects both intermolecular and intramolecular interactions, the decreasing order parameter of vdW only decouples the ligand from the environment and does not change the intramolecular vdW interaction. A restraint is added to prevent the possible bad contacts and to help sampling.