Malaria is a tropical disease caused by infections with protozoan parasites of the genius Plasmodium. Currently, the disease results in over 400,000 human deaths per year worldwide and future prevention and treatment is at risk due to the rise of drug-resistant parasites. Plasmodium falciparum M1 alanyl aminopeptidase is an enzyme involved in the terminal stages of haemoglobin digestion by the intra-erythrocytic stages of the parasite. Chemical inhibition of the enzyme activity prevents the supply of amino acids for parasite development within the blood cells and causes death of malaria parasites. Despite being a promising antimalarial drug target, this enzyme was challenging for inhibitor search using random screenings. One of the reasons is the poorly accessible active site. This project involves computer simulations of the enzyme crystal structures to understand ligand recognition and binding to the buried active site. We demonstrate that electrostatic interactions regulate ligand migration to the active site and offer opportunities for rational design of novel inhibitors.