Molecular dynamics simulations reveal insight into key structural elements of aaptamines as sortase inhibitors with free energy calculations
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- 作者：Zhuo Lv ; Hong S. Wang ; Xiao D. Niu
- 刊名：Chemical Physics Letters
- 出版年：2013
- 出版时间：14 October, 2013
- 年：2013
- 卷：585
- 期：Complete
- 页码：171-177
- 全文大小：2271 K
文摘
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.