Aaptamine (AAP), demethylaaptamine (DAP), isoaaptamine (IAP) and demethyloxyaaptamine (OAP) are known as selective inhibitors of sortase A (SrtA). The energy decomposition analysis indicates that the interactions between the hydroxyl at C-9 of IAP and Glu44 and between the methyl group at the N-1 of IAP and Gly131 are responsible for inhibition and higher potency. The binding energy difference of SrtA-inhibitors contributes to the difference of the IC50 values of inhibitors. These results imply that hydroxyl at C-9 and the methyl group at the N-1 of aaptamine play a key role in the stabilization of the binding of SrtA-inhibitors. (C) 2013 Elsevier B. V. All rights reserved.