RENATE: A Pseudo-retrosynthetic Tool for Synthetically Accessible de novo Design.
RENATE: A Pseudo-retrosynthetic Tool for Synthetically Accessible de novo Design.
复制标题
肾脏：一种用于合成从头设计的伪重生工具。
DOI：
10.1002/minf.202100207
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发表时间：
2022-04
影响因子：
3.6
通讯作者：
Gillet, Valerie J.
中科院分区：
文献类型：
--
作者：
Ghiandoni, Gian Marco;Bodkin, Michael J.;Chen, Beining;Hristozov, Dimitar;Wallace, James E. A.;Webster, James;Gillet, Valerie J.
基于反应的从头设计是指使用从文献中已知反应提取的转化规则生成合成可获得的分子。在这种情况下，我们先前已经描述了从反应数据库中提取反应载体以及它们与用于从起始材料生成新分子的结构生成算法的耦合。当从起始材料设计分子时的一个问题是可以产生的可能产物分子的组合爆炸，特别是对于多步合成。在这里，我们介绍了RENATE的开发，这是一种基于反应的从头设计工具，它基于参考配体的假逆合成片段和从头设计的由内而外的方法。参考配体被片段化;每个片段用于搜索类似片段作为构件;使用反应载体将构件组合成产物;并为每个产物分子建议合成路线。RENATE方法介绍了回顾性验证，以重新创建一组批准的药物。结果表明，RENATE可以生成与相应输入药物非常相似甚至相同的结构，从而验证了该工具中实现的片段化，搜索和设计算法。
Reaction‐based de novo design refers to the generation of synthetically accessible molecules using transformation rules extracted from known reactions in the literature. In this context, we have previously described the extraction of reaction vectors from a reactions database and their coupling with a structure generation algorithm for the generation of novel molecules from a starting material. An issue when designing molecules from a starting material is the combinatorial explosion of possible product molecules that can be generated, especially for multistep syntheses. Here, we present the development of RENATE, a reaction‐based de novo design tool, which is based on a pseudo‐retrosynthetic fragmentation of a reference ligand and an inside‐out approach to de novo design. The reference ligand is fragmented; each fragment is used to search for similar fragments as building blocks; the building blocks are combined into products using reaction vectors; and a synthetic route is suggested for each product molecule. The RENATE methodology is presented followed by a retrospective validation to recreate a set of approved drugs. Results show that RENATE can generate very similar or even identical structures to the corresponding input drugs, hence validating the fragmentation, search, and design heuristics implemented in the tool.
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DOI：
10.1007/978-1-60761-839-3_12
发表时间：
2011-01-01
期刊：
CHEMOINFORMATICS AND COMPUTATIONAL CHEMICAL BIOLOGY
影响因子：
--
作者：
Hartenfeller, Markus;Schneider, Gisbert
通讯作者：
Schneider, Gisbert
影响因子：
5.6
作者：
Patel, Hina;Bodkin, Michael J.;Gillet, Valerie J.
通讯作者：
Gillet, Valerie J.
影响因子：
5.6
作者：
Fechner, U;Schneider, G
通讯作者：
Schneider, G
影响因子：
7.4
作者：
Meyers, Joshua;Fabian, Benedek;Brown, Nathan
通讯作者：
Brown, Nathan
影响因子：
4.1
作者：
Horwood J;Noutahi E
通讯作者：
Noutahi E