High-potency olfactory receptor agonists discovered by virtual high-throughput screening: molecular probes for receptor structure and olfactory function.
High-potency olfactory receptor agonists discovered by virtual high-throughput screening: molecular probes for receptor structure and olfactory function.
复制标题
DOI：
10.1016/j.neuron.2008.11.014
复制
发表时间：
2008-12-10
期刊：
影响因子：
16.2
通讯作者：
Acher, Francine C.
中科院分区：
文献类型：
--
作者：
Triballeau, Nicolas;Van Name, Eric;Laslier, Guillaume;Cai, Diana;Paillard, Guillaume;Sorensen, Peter W.;Hoffmann, Remy;Bertrand, Hugues-Olivier;Ngai, John;Acher, Francine C.
脊椎动物嗅觉系统对不同化学结构的检测和辨别是通过其同源受体识别气味配体来完成的。在本研究中，我们使用了计算的高通量筛选策略，以发现新的嗅觉G蛋白偶联受体的高亲和力激动剂调整识别氨基酸配体。对顶级候选物的功能测试验证了几种激动剂，其效力高于任何受体的已知天然配体。计算模型揭示了这种受体参与配体识别的分子相互作用，并进一步强调了在进化上不同的氨基酸受体中保守的相互作用。值得注意的是，顶级化合物在体内显示出作为气味剂的强大活性，并且包括可用于指示水生环境中细菌存在的天然产物。我们的虚拟筛选方法应适用于新的生物活性分子的鉴定，用于探测体内化学感受器的结构和化学感受系统的功能。
The detection and discrimination of diverse chemical structures by the vertebrate olfactory system is accomplished by the recognition of odorous ligands by their cognate receptors. In the present study we used a computational high-throughput screening strategy to discover novel high affinity agonists of an olfactory G protein-coupled receptor tuned to recognize amino acid ligands. Functional testing of the top candidates validated several agonists with potencies higher than any of the receptor’s known natural ligands. Computational modeling revealed molecular interactions involved in ligand recognition by this receptor, and further highlighted interactions that have been conserved in evolutionarily divergent amino acid receptors. Significantly, the top compounds display robust activities as odorants in vivo, and include a natural product that may be used to signal the presence of bacteria in the aquatic environment. Our virtual screening approach should be applicable to the identification of new bioactive molecules for probing the structure of chemosensory receptors and the function of chemosensory systems in vivo.
登录
查看更多内容
影响因子：
7.3
作者：
Triballeau, N;Acher, F;Bertrand, HO
通讯作者：
Bertrand, HO
影响因子：
3
作者：
Schiniedeberg, Kristin;Shirokova, Elena;Krautwurst, Dietinar
通讯作者：
Krautwurst, Dietinar
影响因子：
7.3
作者：
Bertrand, HO;Bessis, AS;Acher, FC
通讯作者：
Acher, FC
小鼠和大鼠 V2r 鼻鼻受体基因库的组成和进化
影响因子：
4.4
作者：
Yang, H;Shi, P;Zhang, JZ
通讯作者：
Zhang, JZ
DOI：
10.1111/j.1748-1716.1994.tb09800.x
发表时间：
1994-10-01
期刊：
ACTA PHYSIOLOGICA SCANDINAVICA
影响因子：
--
作者：
HARA, TJ
通讯作者：
HARA, TJ