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

The investigations from which SKEMPI data is derived are diverse, spanning many biological processes and reported in 295 publications including systematic scans, alanine and homolog scanning, design studies including computational design and designs derived from phage display, double mutant cycle studies, antibody engineering, biologic drug design and the evaluation of pathological mutations. The largest contribution comes from the group of the late Michael Laskowski Jr., a systematic study of all possible mutations at selected sites in the turkey ovomucoid third domain and its inhibitory interactions with four proteases [43] , as well as studies of interactions of the same domain in other bird species and the design of ultra-high affinity broad-spectrum inhibitors. Substantial data also come from investigations into the inhibitory interactions of class A β-lactamases from the groups of Gideon Schreiber (e.g. [62] ) and Timothy Palzkill (e.g. [10] ), as well as cytokine receptor interactions, in particular studies of type I interferons also from the Schreiber group (e.g. [63] ) and that of K. Christopher Garcia [70] , but also the study of the GM-CSF / GMRα interaction from the group of Michael W. Parker [9] . Other prominent sources of data are studies into hormone receptor interactions, in particular the human growth hormone receptor from the group of Jim Wells (e.g. [14] ) and the prolactin receptor from the group of Michael E. Hodsdon [35] , as well as studies into antigen recognition including the combined computational and experimental design study to enhance affinity of the AQC2 antibody to integrin α-1 from the group of Herman Van Vlijmen [12] , the dissection of the interactions of broadly neutralising antibodies targeting HIV gp120 [11] from the group of Richard A. Friesner, and various investigations from the group of Roy A. Mariuzza (e.g. [15] ). Also notable is the alanine scanning of the urokinase-type plasminogen activator and its receptor from the group of Michael Ploug [21] , studies of Ras effector interactions from the group of Christian Herrmann (e.g. [34] ), investigations of pMHC/TCR interactions from the group of Brian Baker (e.g. [59] ), and investigations into the congate and non-cognate recognition of E. coli colicin DNase bacteriotoxins by their immunity proteins from the group of Colin Kleanthous (e.g. [40] ).