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

Protein-protein interactions are central to almost all biological processes, from cellular signal transduction and the assembly of mesoscopic structures such as myofilaments, to viral adhesion and the immune response. Consequently the effects of changes in protein sequence on the structure, thermodynamics and kinetics of protein-protein interactions has wide implications for constraining the permissible substitutions that accrue over the course of evolution, and for understanding the molecular etiology of disease. Methods which measure, predict or optimise these changes have applications in designing de novo interactions [20] , enhancing the specificity and affinity of biological therapeutics (e.g. [3] ), designing combinatorial protein libraries (e.g. [24] ), uncovering the effects of pathological mutations (e.g. [72] ), locating druggable binding sites (e.g. [68] ) and binding hotspots for drug design [25] , altering binding kinetics [13] , [64] , protein-protein docking (e.g. [19] ), and characterising transition states (e.g. [75] ), binding pathways [61] , and sequence-affinity landscapes [2] .