Fig. 14.

Differentiation of the communication paths traced by the averaged EC hubs (labeled), starting from the allosteric ligand towards the catalytic residue. The protease is represented as a cartoon, onto which the averaged EC hub residues are overlaid as sphere representations, together with the non-hub catalytic residues HIS41 and CYS145 (in orange spheres). The top panels show the hubs obtained in (A) the SANC00302-bound reference M^pro, and (B) the SANC00302-bound G71S mutant. The bottom panels show the hubs obtained in (C) the SANC00468-bound reference M^pro, and (D) the SANC00468-bound A173V mutant. Compounds SANC00302 and SANC00468, the positions of which are as observed after MD simulation, are depicted as green and purple stick figure representations respectively. The mutation loci are represented as purple spheres and are each indicated by an arrow. Additional hubs in the two ligand-bound reference proteins include residues LEU115, ALA116 and CYS117 in the case of panel (A), and residues LEU115, ALA116, CYS117, PRO122, GLY124 and VAL125 in panel (C), but are not shown as labels, for improved visibility. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)