How broadly tuned olfactory receptors equally recognize their agonists. Human OR1G1 as a test case
How broadly tuned olfactory receptors equally recognize their agonists. Human OR1G1 as a test case
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DOI：
10.1007/s00018-012-1116-0
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发表时间：
2012-12-01
影响因子：
8
通讯作者：
Golebiowski, Jerome
中科院分区：
文献类型：
--
作者：
Charlier, Landry;Topin, Jeremie;Golebiowski, Jerome
通过结合细胞生物学、钙成像和分子建模的联合方法，分析了由广泛调谐的嗅觉受体主导激动剂结合模式的分子特征。的气味/受体的亲和力，估计通过分子动力学模拟过程中积累的统计数据，是根据实验排名。尽管在许多系统中，受体通过定向相互作用的网络（例如H键合）来识别它们的靶标，但是通过广泛调谐的嗅觉受体的结合由非极性项主导。我们展示了这样的功能如何允许属于不同化学家族的化学物质通过补偿结合位点内的相互作用来类似地激活受体。
The molecular features that dominate the binding mode of agonists by a broadly tuned olfactory receptor are analyzed through a joint approach combining cell biology, calcium imaging, and molecular modeling. The odorant/receptor affinities, estimated through statistics accrued during molecular dynamics simulations, are in accordance with the experimental ranking. Although in many systems receptors recognize their target through a network of oriented interactions, such as H-bonding, the binding by broadly tuned olfactory receptors is dominated by non-polar terms. We show how such a feature allows chemicals belonging to different chemical families to similarly activate the receptors through compensations of interactions within the binding site.