On the use of orientational restraints and symmetry corrections in alchemical free energy calculations

David L. Mobley, John D. Chodera, and Ken A. Dill.
J. Chem. Phys. 125:084902, 2006. [DOI] [PDF]

We illustrate how orientational restraints can be used to greatly reduce the computational effort in alchemical calculations of ligand binding free energies, and clarify how symmetry corrections are necessary when molecules contain symmetric or pseudosymmetric substituents.