The data presented here extend our previous computational investigations of MCR-1 by considering, for the first time, the dynamic behavior of the full-length enzyme in a model membrane environment. Over extended (500 ns) simulations of MCR-1 in mono-and di-zinc forms, in both the unmodified "resting" and phosphointermediate forms, the protein is characterized by a relatively limited degree of interdomain flexibility that is consistent across the different states and is little affected by the presence of the POPE donor substrate. In simulations that include bound POPE in the starting structure, POPE remains associated throughout the duration of the trajectories, but the head group samples a range of orientations in the different complexes. In simulations of the "resting" unmodified mono-zinc enzyme bound POPE is however able to access a stable conformation, with its PEtN head group close to the Thr285 acceptor, that we consider represents a plausible ground state complex for the first stage of the PEtN transfer reaction, i.e. phosphointermediate formation. This supports the contention that the mono-zinc form of MCR-1 is able to accept PEtN from a lipidated donor such as POPE and form the phosphointermediate. The relative stability of the Zn1 site in the different complexes contrasts with the instability of the Zn2 site under all conditions trialed, though we caution that the accuracy of such simulations is limited by the well-known challenges of parameterizing transition metal ions such as zinc for molecular dynamics simulations , and the metalation state(s) of full-length MCR-1, particularly in the phosphointermediate form, warrant further exploration at higher (quantum mechanical, QM) levels of theory. Extending such investigations to explore the interaction of MCR-1 (and/or related PEtN transferases) with the lipid A acceptor substrate will then represent an important next step in understanding the activity of this increasingly important antimicrobial resistance determinant.