The inhibition of insulin-regulated aminopeptidase (IRAP) has been demonstrated to increase levels of neuroactive peptides in the brain, thereby enhancing long-term potentiation and improving memory retention. In this study, enhanced sampling QM/MM MD simulations were employed to elucidate the free energy landscape underlying the differential hydrolisis of the natural substrate oxytocin and the prototypical peptide inhibitor angiotensin IV by IRAP.