These analyses indicate that the complete MCR-1 bound system retains a conformation close to that of the starting structure throughout the duration of the simulations; i.e. that both the structures of the individual domains, and their orientations relative to one another, are largely preserved during 500 ns of MD simulations in this model membrane environment. To further verify the latter conclusion, the distances between the respective centers of mass of the catalytic domain (residues 219 -541) and transmembrane domain (residues 11 -218) were plotted over time (50 -500 ns) as averages ± 2 standard deviations (Figure ). Consistent with analysis of C RMSD values, the interdomain distance remains within a constant range throughout the simulations, providing no evidence that, over a time scale of 500 ns, changes in zinc stoichiometry, PEtN addition to Thr285, or presence/absence of the POPE donor substrate result in global changes to MCR-1 conformation. Specifically, none of our simulations identify the substantial changes in interdomain distance that would be expected were MCR-1 to be undergoing conformational transitions involving large-scale motions of the catalytic relative to the transmembrane domain, as previously observed in EptA . As shown in Figure , while some variation in domain positions in the individual simulations is evident, reflecting both repositioning of the transmembrane domain within the membrane and some limited reorientation of the two domains relative to one another, we do not observe the loss of interdomain interactions, and close association of the periplasmic domain with the membrane surface, described by Anandan et al in their studies of N. meningitidis EptA .