where ∆G Rest. Scheme collects any additional terms which are specific to the restraints scheme used. The relevant restraints scheme for each form of ∆G Rest. Scheme is shown on the right of Equation : "Boresch" includes both Boresch restraints and the "non-rigorous" implementation of multiple distance restraints shown in Figure For calculations where multiple distance restraints were released to a single distance restraint, ∆G o Release was calculated by numerical integration of Equation 11, and the force constants were scaled with λ 5 over 21 evenly-spaced λ windows. The same protocol was used to introduce and remove all restraints in the multiple distance restraints simulations with intramolecular restraints.