SCUBIDOO: A Large yet Screenable and Easily Searchable Database of Computationally Created Chemical Compounds Optimized toward High Likelihood of Synthetic Tractability
SCUBIDOO: A Large yet Screenable and Easily Searchable Database of Computationally Created Chemical Compounds Optimized toward High Likelihood of Synthetic Tractability
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DOI：
10.1021/acs.jcim.5b00203
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发表时间：
2015-09-01
影响因子：
5.6
通讯作者：
Kolb, P.
中科院分区：
文献类型：
--
作者：
Chevillard, F.;Kolb, P.
新的药物设计被广泛地辅助计算方法，使在短时间内产生大量的新的虚拟分子。虽然计算生成的化合物的新颖性可以很容易地评估，但这种方法往往忽略了分子的合成可行性，从而造成了潜在的障碍，可能成为进一步研究的障碍。因此，我们开发了SCUBIDOO，这是一个免费访问的数据库概念，目前拥有2100万个虚拟产品，这些产品来自一个小型的构建模块库和一系列强大的有机反应。这个大数据集被简化为三个具有代表性且计算易于处理的样本，分别表示为S、M和L，包含9994、99977和999794个产品。这些小集合可以作为配体识别和优化项目的起点。生成的产品带有合成说明和可能的副反应警报，我们表明它们表现出类似药物的特性，同时仍然延伸到化学空间的未探索象限，从而表明了新颖性。我们将展示多个示例，演示SCUBIDOO如何简化围绕初始命中的搜索。这个数据库可能是早期配体发现项目的一个有用的想法发生器，因为它允许关注那些可能是合成可行的分子，因此可以进一步研究。再加上其模块化的构建模块的原则，该数据库也适用于结构活动关系研究或片段增长策略。
De nova drug design is widely assisted by computational approaches that enable the generation of a tremendous amount of new virtual molecules within a short time frame. While the novelty of the computationally generated compounds can easily be assessed, such approaches often neglect the synthetic feasibility of the molecules, thus creating a potential hurdle that can be a barrier to further investigation. Therefore, we have developed SCUBIDOO, a freely accessible database concept that currently holds 21 million virtual products originating from a small library of building blocks and a collection of robust organic reactions. This large data set was reduced to three representative and computationally tractable samples denoted as S, M, and L, containing 9994, 99977, and 999 794 products, respectively. These small sets are useful as starting points for ligand identification and optimization projects. The generated products come with synthesis instructions and alerts of possible side reactions, and we show that they exhibit drug-like properties while still extending into unexplored quadrants of chemical space, thus suggesting novelty. We show multiple examples that demonstrate how SCUBIDOO can facilitate the search around initial hits. This database might be a useful idea generator for early ligand discovery projects since it allows a focus on those molecules that are likely to be synthetically feasible and can therefore be studied further. Together with its modular building block construction principle, this database is also suitable for structure activity relationship studies or fragment-growing strategies.