Fig. 4

Distribution of drug–mutation relationships on the reference protein kinase A (PKA) crystal structure and interaction analyses. a Interaction hot spots are labeled and represented by larger spheres on the reference PKA structure (PDB ID: 1ATP). If a residue is involved in multiple drug–mutation relationships, the median of their impacts on \(\hbox {IC}_{50}\) is chosen to represent the color of the sphere. Red sphere represents drug–mutation relationship with a positive impact on \(\hbox {IC}_{50}\); blue sphere represents relationship with a negative impact on \(\hbox {IC}_{50}\). b, c represent examples of two PKIs (afatinib and lapatinib) with different binding modes in the active (PDB ID: 4G5J) and inactive (PDB ID: 1XKK) conformations of EGFR, respectively. The residue corresponding to EGFR L858 (PKA_187) is labeled in each example; the mutant form (arginine) modeled in PyMol [78] is shown. d, e represent statistical interaction analyses for Fingerprint_791 versus PKA_187_CHA and Fingerprint_826 versus PKA_187_VOL in the NSCLC dataset, respectively