From desktop to benchtop with automated computational workflows for computer-aided design in asymmetric catalysis
From desktop to benchtop with automated computational workflows for computer-aided design in asymmetric catalysis
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DOI：
10.1038/s41929-020-0468-3
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发表时间：
2020-07-01
期刊：
影响因子：
37.8
通讯作者：
Moitessier, Nicolas
中科院分区：
文献类型：
--
作者：
Burai Patrascu, Mihai;Pottel, Joshua;Moitessier, Nicolas
有机化学家的工具箱非常庞大，其中包含加速新型化学物质合成的技术。不对称催化领域是进入化学空间新领域的一种方法，如今的计算能力足以协助这一探索。不幸的是，现有技术通常需要计算专业知识，因此在合成化学中未得到充分利用。在这里，我们展示了我们的平台虚拟化学家，实验室化学家只需点击几下鼠标即可在实验室测试之前预测不对称化学反应的结果。模块化工作流程有助于模拟各种实验，包括所讨论的四种现实场景：一对一设计、文库筛选、命中优化和底物范围评估。候选催化剂可在数小时内筛选完毕，与随机测试相比，对映选择性预测提供了实质性的丰富。达到~1 kcal mol(-1)以内的精度为不对称催化剂设计领域的计算化学提供了机会，使实验室化学家能够指导不对称催化剂的设计和发现。计算化学在很大程度上仍然是实验化学界无法接触到的。在这里，我们报告了 VIRTUAL CHEMIST，这是一款免费供学术使用的软件套件，它使没有计算化学专业知识的有机化学家能够进行虚拟筛选实验，以发现和设计不对称催化剂。
The organic chemist's toolbox is vast, with technologies to accelerate the synthesis of novel chemical matter. The field of asymmetric catalysis is one approach to accessing new areas of chemical space and computational power is today sufficient to assist in this exploration. Unfortunately, existing techniques generally require computational expertise and are therefore underutilized in synthetic chemistry. Here we present our platformVirtual Chemist, which allows bench chemists to predict outcomes of asymmetric chemical reactions ahead of testing in the laboratory, in just a few clicks. Modular workflows facilitate the simulation of various sets of experiments, including the four realistic scenarios discussed: one-by-one design, library screening, hit optimization and substrate-scope evaluation. Catalyst candidates are screened within hours and the enantioselectivity predictions provide substantial enrichments compared to random testing. The achieved accuracies within ~1 kcal mol(-1)provide opportunities for computational chemistry in the field of asymmetric catalyst design, allowing bench chemists to guide the design and discovery of asymmetric catalysts.Computational chemistry has remained largely inaccessible to the experimental chemistry community. Here we report the VIRTUAL CHEMIST, a software suite free for academic use, that enables organic chemists without expertise in computational chemistry to perform virtual screening experiments for asymmetric catalyst discovery and design.