Structure and reaction based evaluation of synthetic accessibility
Structure and reaction based evaluation of synthetic accessibility
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DOI：
10.1007/s10822-006-9099-2
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发表时间：
2007-06-01
影响因子：
3.5
通讯作者：
Gasteiger, Johann
中科院分区：
文献类型：
--
作者：
Boda, Krisztina;Seidel, Thomas;Gasteiger, Johann
从头设计系统提供了强大的方法来建议一组具有高估计结合亲和力的新结构。这些方法的一个缺点是，一些所建议的结构只能很困难地合成。我们设计了一种评分方法，根据结构复杂性、与现有起始材料的相似性以及对战略键的评估，快速评估结构的合成可达性，在战略键评估中，结构可以被分解以获得更简单的碎片。这些单独的组成部分通过一个相加方案被组合成综合可达性的总体分数。根据药物化学家的可及性得分，通过线性回归分析计算得分函数各组成部分的权重。合成可及性的计算值与化学家提出的值在某种程度上是一致的，这与化学家彼此之间的一致程度相当。
De novo design systems provide powerful methods to suggest a set of novel structures with high estimated binding affinity. One deficiency of these methods is that some of the suggested structures could be synthesized only with great difficulty. We devised a scoring method that rapidly evaluates synthetic accessibility of structures based on structural complexity, similarity to available starting materials and assessment of strategic bonds where a structure can be decomposed to obtain simpler fragments. These individual components were combined to an overall score of synthetic accessibility by an additive scheme. The weights of the scoring function components were calculated by linear regression analysis based on accessibility scores derived from medicinal chemists. The calculated values for synthetic accessibility agree with the values proposed by chemists to an extent that compares well with how chemists agree with each other.