As noted earlier, site C is the crystallographically defined site of ADP ribose and has the most negative binding affinity for tofacitinib. This relatively high thermodynamic stability at site C is also reflected in the occupancy maps and ligand-residue contact frequency distribution plots of sub-replicas initiated from the end frame of replica 20 as shown in Figure . The ligand possesses a well-defined pose across all replicas when initiated from site C (sub-replicas of replica 20). This is contrary to the behaviour seen when initiating sub-replicas from the ligand located in other binding sites where the ligand explores multiple sites over each set of sub-replicas as also evident from Figure . Overall, this provides evidence that tofacitinib would act to competitively inhibit the protein.