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

SKEMPI is a manually curated database of mutations in structurally characterised protein-protein interactions and the effect of those mutations on binding affinity and other parameters [47] . The first release has been used as a basis for many further studies, including the development of energy functions [48] , [46] which were subsequently implemented in the CCharPPI web server for characterising protein-protein interactions [49] , as well as being used for ranking docked poses [45] , [58] , [6] , [50] . SKEMPI has also been used to study human disease [56] , [16] , [55] , assessing the role of dynamics on binding [69] , exploring the conservation of binding regions [28] , evaluating experimental affinity measurement methods [22] , as well serving as a data source for models which predict dissociation rate changes upon mutation [1] , pathological mutations [23] , hotspot residues (e.g. [30] , [44] , [42] , [66] ) and changes in binding energy (e.g. [60] , [17] , [78] , [7] , [53] , [51] , [57] , [18] , [39] , [76] , [54] , [77] , [37] , [5] ). Here we present a major update to the benchmark in terms of the number of mutations in the database and the number of different systems included (Table I) . We now also include details of the experimental method for all entries, based on the categories of [22] , as well as mutations which abolished detectable binding or for which only an upper or lower affinity limit could be ascertained for the wild-type or mutant.