Malaria remains a major health challenge throughout the world. In the malaria parasite, inhibition of the Plasmodium falciparum M17 aminopeptidase (PfA-M17) has been shown to kill parasites in vitro and in vivo. The PfA-M17 aminopeptidase is postulated to form part of the proteolytic cascade that digests human haemoglobin, as well as an as yet known role in the early stages of parasite development. Previous crystallographic and functional studies have shown that PfA-M17 is hexameric, formed by a dimer of homo-trimers. The functional role of the hexameric formation in catalytic mechanism and regulation remains to be determined. Here, we have used Normal Mode Analysis (NMA) and Molecular Dynamics simulations (MD) to study the movements of PfA-M17 protein. To undertake this work, we had to calculate a new MD force field to study the di-cation containing catalytic domain of PfA-M17. We have used a quantum mechanics approach to validate this new force field and show that it is suitable to analyse the M17 superfamily. Our results reveal previously unknown coordinated motion between the two trimers within the hexamer, suggesting communication between the sub-units. Here we present out latest results and propose a substrate mechanism based on our current in silico approaches. The results provide fundamental new knowledge of the M17 superfamily and will be beneficial to future selective inhibitor design of PfA-M17.