Additional costs associated with rigorous multiple distance restraints schemes may be compensated for by convergence benefits in some systems, although that was not demonstrated in this work. The mean ∆G o Bound calculated based on pose A with rigorous implementations of multiple distance restraints (-6.16 ± 1.43 kcal mol -1 ) was in close agreement with the mean result calculated with Boresch restraints (-6.28 ± 0.49 kcal mol -1 ).