Flux (1): A virtual synthesis scheme for fragment-based de novo design
Flux (1): A virtual synthesis scheme for fragment-based de novo design
复制标题
DOI：
10.1021/ci0503560
复制
发表时间：
2006-03-01
影响因子：
5.6
通讯作者：
Schneider, G
中科院分区：
文献类型：
--
作者：
Fechner, U;Schneider, G
它表明，通过应用简单的伪逆合成的药物样分子的碎片的结果在化学上有意义的从头分子生成的积木的股票。随机搜索算法结合基于配体的相似性评分（Flux：基于片段的配体构建器推理）促进使用单一已知参考化合物作为模板产生新分子。这种分子组装方法适用于缺乏受体结构信息的情况。在一项案例研究中，我们使用伊马替尼（Gleevec）和因子Xa抑制剂作为参考结构。该算法成功地从头开始重新设计模板，并提出了几种替代的分子结构。由此产生的设计分子是化学合理的，并包含必要的子结构基序。分子描述符的比较表明，全息描述符可能是基于配体的从头设计的二进制指纹。
It is demonstrated that the fragmentation of druglike molecules by applying simplistic pseudo-retrosynthesis results in a stock of chemically meaningful building blocks for de novo molecule generation. A stochastic search algorithm in conjunction with ligand-based similarity scoring (Flux: fragment-based ligand builder reaxions) facilitated the generation of new molecules using a sin g le known reference compound as a template. This molecule assembly method is applicable in the absence of receptor-structure information. In a case study, we used imantinib (Gleevec) and a Factor Xa inhibitor as the reference structures. The algorithm succeeded in redesigning the templates from scratch and suggested several alternative molecular structures. The resulting designed molecules were chemically reasonable and contained essential substructure motifs. A comparison of molecular descriptors suggests that holographic descriptors might be advantaceous over binary fingerprints for ligand-based de novo design.