Molecular dynamics and free energy studies of chirality specificity effects on aminobenzo[a]quinolizine inhibitors binding to DPP-IV
Molecular dynamics and free energy studies of chirality specificity effects on aminobenzo[a]quinolizine inhibitors binding to DPP-IV
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氨基苯并[a]喹嗪抑制剂与 DPP-IV 结合的手性特异性影响的分子动力学和自由能研究
DOI：
10.1007/s00894-012-1653-3
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发表时间：
2013-03
影响因子：
2.2
通讯作者：
Ji Mingjuan
中科院分区：
文献类型：
--
作者：
Gao Jian;Luo Fang;Geng Lingling;Ji Mingjuan
AbstractThe aminobenzo[a]quinolizines were investigated as a novel class of DPP-IV inhibitors. The stereochemistry of this class plays an important role in the bioactivity. In this study, the mechanisms of how different configuration of three chiral centers of this class influences the binding affinity were investigated by molecular dynamics simulations, free energy decomposition analysis. The S configuration for chiral center 3* is decisive for isomers to maintain high bioactivity; the chirality effect of chiral center 2* on the binding affinity is largely dependent, while the S configuration for chiral center 2* is preferable to R configuration for the bioactivity gain; the effect of chiral center 11b* on the binding affinity is insignificant. The chirality specificity for three chiral centers is responsible for distinction of two van der Waals contacts with Tyr547 and Phe357, and of H-bonding interactions with Arg125 and Glu206. Particularly, the Arg125 to act as a bridge in the H-bonding network contributes to stable H-bonding interactions of isomer in DPP-IV active site.
FigureThe S configuration for chiral center 3* is decisive for high bioactivity; the chirality effect of chiral center 2* on binding affinity is largely dependent, while the S configuration for 2* is preferable to R for bioactivity gain; the chirality specificity for chiral center 11b* to binding affinity is insignificant.
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影响因子：
6.1
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Deacon, Carolyn F.
通讯作者：
Deacon, Carolyn F.
影响因子：
7.7
作者：
Kim, Su-Jin;Nian, Cuilan;McIntosh, Christopher H. S.
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McIntosh, Christopher H. S.
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3
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Gohlke, H;Case, DA
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Case, DA
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4.4
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Hou, TJ;McLaughlin, W;Wang, W
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J. Weiser;P. Shenkin;W. Still
通讯作者：
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