Molecular structures enumeration and virtual screening in the chemical space with RetroPath2.0.
Molecular structures enumeration and virtual screening in the chemical space with RetroPath2.0.
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DOI：
10.1186/s13321-017-0252-9
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发表时间：
2017-12-19
影响因子：
8.6
通讯作者：
Faulon JL
中科院分区：
文献类型：
--
作者：
Koch M;Duigou T;Carbonell P;Faulon JL
结合化学反应规则的网络生成工具主要用于合成规划，最近用于代谢工程。使用相同的核心算法，这些工具将一组规则应用于化合物的源集合，当产生化合物的汇集合时停止。当使用适当的接收器、源和规则时，该核心算法可以用于各种应用程序，而不仅仅是它所开发的那些应用程序。在这里，我们展示了开源工作流RetroPath2.0的使用。首先，我们在数学上证明，我们可以生成一个分子的所有结构异构体使用一组减少的反应规则。然后，我们使用这种枚举策略来筛选一组单体周围的化学空间，并预测它们的玻璃化转变温度，以及氨基糖苷类药物周围的结构，以最大限度地提高抗菌活性。我们还使用酶反应规则对氨基糖苷类进行筛选，以确保生物合成的可及性。最后，我们在E上使用我们的工作流程。coli模型，以完成E.大肠杆菌代谢物组，与新的分子产生使用混杂的酶促反应规则。这些新的分子上搜索的MS光谱的E。通过KNIME分析平台将我们的工作流程与OpenMS连接起来。我们提供了一个易于使用和修改，模块化和开源的工作流程。我们通过各种用例展示了它的多功能性，包括分子结构枚举，化学空间中的虚拟筛选和代谢组完成。因为它是开源的，并且可以在MyExperiment.org上免费获得，所以工作流社区的贡献可能会进一步扩展该工具的功能，甚至超出本文中提出的用例。本文的在线版本（10.1186/s13321-017-0252-9）包含补充材料，可供授权用户使用。
Network generation tools coupled with chemical reaction rules have been mainly developed for synthesis planning and more recently for metabolic engineering. Using the same core algorithm, these tools apply a set of rules to a source set of compounds, stopping when a sink set of compounds has been produced. When using the appropriate sink, source and rules, this core algorithm can be used for a variety of applications beyond those it has been developed for. Here, we showcase the use of the open source workflow RetroPath2.0. First, we mathematically prove that we can generate all structural isomers of a molecule using a reduced set of reaction rules. We then use this enumeration strategy to screen the chemical space around a set of monomers and predict their glass transition temperatures, as well as around aminoglycosides to search structures maximizing antibacterial activity. We also perform a screening around aminoglycosides with enzymatic reaction rules to ensure biosynthetic accessibility. We finally use our workflow on an E. coli model to complete E. coli metabolome, with novel molecules generated using promiscuous enzymatic reaction rules. These novel molecules are searched on the MS spectra of an E. coli cell lysate interfacing our workflow with OpenMS through the KNIME Analytics Platform. We provide an easy to use and modify, modular, and open-source workflow. We demonstrate its versatility through a variety of use cases including molecular structure enumeration, virtual screening in the chemical space, and metabolome completion. Because it is open source and freely available on MyExperiment.org, workflow community contributions should likely expand further the features of the tool, even beyond the use cases presented in the paper. The online version of this article (10.1186/s13321-017-0252-9) contains supplementary material, which is available to authorized users.
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DOI：
10.1021/ci010132r
发表时间：
2002-11-01
期刊：
JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES
影响因子：
--
作者：
Durant, JL;Leland, BA;Nourse, JG
通讯作者：
Nourse, JG
影响因子：
9.9
作者：
Orth, Jeffrey D.;Conrad, Tom M.;Na, Jessica;Lerman, Joshua A.;Nam, Hojung;Feist, Adam M.;Palsson, Bernhard O.
通讯作者：
Palsson, Bernhard O.
影响因子：
3.6
作者：
Gally, Jose-Manuel;Bourg, Stephane;Bonnet, Pascal
通讯作者：
Bonnet, Pascal
影响因子：
5.6
作者：
Kawai, Kentaro;Nagata, Naoya;Takahashi, Yoshimasa
通讯作者：
Takahashi, Yoshimasa
影响因子：
5.6
作者：
Martin, Shawn
通讯作者：
Martin, Shawn