SKEMPI 2.0: An updated benchmark of changes in protein-protein binding energy, kinetics and thermodynamics upon mutation

Justina Jankauskaite; Brian Jiménez-García; Justas Dapkunas; Juan Fernández-Recio; Iain H. Moal

Higher order interaction terms can be garnered from higher cycles, such as triple mutant cubes, constructed from the energies of the wild-type, three single mutants, three corresponding double mutants and the triple mutant [26] . In SKEMPI, 45 triple mutant cubes can be made, with 10 coming from the same reference. For these, third order interaction energies fall within the -1 to 1 kcal.mol −1 range. For fourth order interactions, constructed from energies of the wild-type, four single mutants, six double mutants, four triple mutants and the quadruple mutant, 14 examples exist within SKEMPI. However, care should be taken in ascribing meaning to fourth order residue coupling energies due to the accumulations of errors, which in these cases are exacerbated by the affinities having been reported in different publications. No fifth or higher order interactions are present.