Molecular Determinants Underlying Binding Specificities of the ABL Kinase Inhibitors: Combining Alanine Scanning of Binding Hot Spots with Network Analysis of Residue Interactions and Coevolution
Fig 15
The Network Analysis of Coevolving Residues: Residue Connectivity and Structural Mapping onto Kinase Structures.
The network connectivity of coevolving residue pairs is shown by a sequential circular representation of the MSA. The labels in the first (outer) circle indicate the alignment position and the amino acid code of the reference sequence. The colored square boxes of the second circle indicate the MSA position conservation (highly conserved positions are in red, while less conserved ones are in blue).The third and fourth circles show the pMI (pMI) and cMI values as histograms, facing inwards and outwards respectively. Each node represents a position in the MSA and lines between nodes in the circle connect pairs of positions with MI > 6.5 as defined by MISTIC program [130]. Node color represents site conservation: red for highly conserved sites and blue for less conserved sites.