Large-scale automated crystallography screening of fragments carried out by Keedy2018 et al. has resulted in a tethered fragment 3 at a site distinct from that occupied by compounds 1-2. The fragment is covalently linked to a K197C mutant and shows 60% maximum inhibition . A ligand binding at the K197 site may interact with residues part of the allosteric network, such as Y152 or N193 . Therefore, the joint sMD/MSM protocol was applied to compound 3. The model produced a down-shift in active conformation probability distribution with respect to the reference system (Figure 3"), suggesting an inhibitory effect intermediate between 1 and 2.