Decoupling and annihilation

The terms decoupling and annihilation have been used in somewhat confusing ways in the free energy literature, so we want to clarify the definitions we use. In our terminology, decoupling of an molecular interaction refers to turning off that interaction between that molecule and its environment. Annihilation of a molecular interaction refers to turning off that interaction entirely.

For example, one could take a benzene molecule in water, with its partial charges set to zero, and turn off its Lennard-Jones interactions with its water environment, leaving on its intramolecular Lennard-Jones interactions); this is decoupling. Alternatively, one could take the same molecule, and turn off its Lennard-Jones interactions entirely (including its intramolecular Lennard-Jones interactions); this is annihilation.

The usage we are avoiding is the terminology double decoupling method and double annihilation method to refer to whether or not restraints are used in absolute binding free energy calculations. In our view this is confusing, since annihilation and decoupling can also be used in the way described above. We will, therefore, only use annihilation and decoupling in the way just described, and distinguish between the two methods just named by simply refering to whether or not restraints are employed.