The sensitivity of the E-loop to changes in the WPD-loop is consistent with a recent NMR study and our recent work in which we identified that the dynamics of these loops were correlated with one another. Likewise, Loop 11 is part of a previously characterized allosteric network which modulates the WPD-loop conformation. Moving from Chimera 4 to Chimera 3, we observe further destabilization of both the WPD-and E-loop, and in particular at the N-terminal portion of the WPD-loop. Given the nature and location of the mutation that separates Chimeras 4 and 3 (T177G, located at the N-terminus of the WPD-loop) it is perhaps not surprising to see this effect. Finally, differences in stability are observed between Chimera 3 and Chimera 1 and are located towards Loop 11 and the α7-helix. It is unclear from the H-bond networks how these two mutations (P185V and E186S) that separate Chimera 3 and Chimera 1 have resulted in altered stabilities at Loop 11 and the α7-helix, these changes may be due to alterations in a different type of non-covalent interaction(s).