Knowledge-Based Approach to de Novo Design Using Reaction Vectors
Knowledge-Based Approach to de Novo Design Using Reaction Vectors
复制标题
DOI：
10.1021/ci800413m
复制
发表时间：
2009-05-01
影响因子：
5.6
通讯作者：
Gillet, Valerie J.
中科院分区：
文献类型：
--
作者：
Patel, Hina;Bodkin, Michael J.;Gillet, Valerie J.
描述了一种基于知识的方法来从头设计合成可行的分子。该方法基于反应矢量，其表示随着反应发生的环境而在反应中心沿着发生的结构变化。反应向量是从反应的数据库中自动导出的，该数据库不受大小或反应复杂性的限制。已经开发了一种结构生成算法，从而可以将反应向量应用于以前看不见的起始材料，以提出新的合成。该方法已在KNIME中实施，并通过复制已知的合成路线进行了验证。然后，我们提出了应用程序的方法在不同的药物设计方案，包括铅优化和库枚举。该方法提供了巨大的潜力，捕捉和使用越来越多的数据，通过电子实验室笔记本电脑的反应。
A knowledge-based approach to the de novo design of synthetically feasible molecules is described. The method is based on reaction vectors which represent the structural changes that take place at the reaction center along with the environment in which the reaction occurs. The reaction vectors are derived automatically from a database of reactions which is not restricted by size or reaction complexity. A structure generation algorithm has been developed whereby reaction vectors can be applied to previously unseen starting materials in order to suggest novel syntheses. The approach has been implemented in KNIME and is validated by reproducing known synthetic routes. We then present applications of the method in different drug design scenarios including lead optimization and library enumeration. The method offers great potential for capturing and using the growing body of data on reactions that is becoming available through electronic laboratory notebooks.