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

Defining homologous interactions: Each entry also specifies which other entries are mutations to homologous interactions. Two interactions are deemed homologous if they have a shared binding partner or homologous binding partner and at least 70% of the corresponding interface residues are common to both interactions. We determine the homology between proteins using the GAP4 program [29] , and define homologous proteins as those with a similarity score greater than 50 and at least 30% sequence identity. Interface residues are defined as those with a non-hydrogen atom within 10Å of a non-hydrogen atom on the binding partner. Interactions falling within manually assigned clusters of homologous interactions are designated as pMHC/TCR, antibody/antigen or protease/inhibitor. While the names of these clusters have been chosen to reflect the predominant function of their constituent interactions, they reflect the homologies within the data set and are not functional assignments. Thus, for instance, some nanobodies are classified as antibodies as they bind to the same site as cetuximab, 14.3.d is classified as TCR, even though it is only the β chain, and its binding partner, enterotoxin C3, is classified as a pMHC.