when binding of the ligand is dynamically accessible -e.g., the binding pocket is hidden in certain conformations (this may be associated with allosteric regulation and other induced conformational changes); (b) the need for including finite temperature effects (such as relevant entropic contributions). To what extent do you think that your approach takes these two factors into account? Would you therefore expect it to be adequate for any possible PL system, or perhaps just for a particular subclass of PL interactions?