Malaria is a major cause of global morbidity and mortality. Chemotherapy remains our best choice in controlling the disease. However, current therapeutics and prophylactics for malaria are under massive challenge due to the emergence of drug-resistant parasites. Our lab focuses on one of the main human malaria parasites, Plasmodium falciparum, which expresses two neutral aminopeptidases, PfA-M1 and PfA-M17. Both aminopeptidases generate free amino acids in the very last step of the digestion of hemoglobin and are required for the survival of the parasites. Earlier studies have shown that they can efficiently cleave N-terminal amino acids from peptide substrates. Therefore, in order to block the formation of the intracellular pool of amino acids available to the parasite, our lab has designed and tested many dipeptide analogs as potential inhibitors. The effectiveness of these inhibitors varied as the result of the specificities of PfA-M1 and PfA-M17 towards different peptide substrates. PfA-M1 exhibits a remarkably wider substrate specificity than PfA-M17. In contrast, PfA-M17 possesses a severely restricted specificity for N-terminally exposed small, hydrophobic amino acids. To further understand and increase our knowledge of how these aminopeptidases function, we will perform a comprehensive molecular dynamics study. The findings of this study will contribute to future rational drug design for novel antimalarials