送神经网络用于预测非对称Negishi反应的酶选择性
Abbigayle E Cuomo1, Sebastian Ibarraran1, Sanil Sreekumar2
1Department of Chemistry, Yale University, New Haven, Connecticut 06511, United States.
ACS central science
|October 2, 2023
概括
这项研究使用密度功能理论 (DFT) 过渡状态 (TS) 数据训练神经网络,以预测化学合成中的enantioselectivity,即使使用小数据集.
科学领域:
- 计算化学计算化学
- 有机合成 有机合成
- 机器学习 机器学习
背景情况:
- 密度函数理论 (DFT) 对于预测化学反应选择性至关重要.
- 预测复杂合成中的选择性是具有挑战性的,因为能量差异很小.
- 数据科学提供了互补的方法,但与有限的有机合成数据集作斗争.
研究的目的:
- 开发一种机器学习模型,用于预测Negishi交叉合反应中的酶选择性.
- 调查DFT衍生特征对于在小数据集上训练神经网络的实用性.
- 为了将这种DFT增强的机器学习方法与传统方法进行比较.
主要方法:
- 使用DFT计算来获得过渡状态 (TS) 能量.
- 来自DFT TS计算的工程特征来标记一个小数据集.
- 训练了一个前神经网络来预测enantioselectivity.
- 对神经网络中DFT能量和连接体/基态特征进行性能比较.
主要成果:
- 在DFT TS上训练的前神经网络特征成功预测了enantioselectivity.
- 这种方法即使在有限的数据集上也被证明是有效的.
- 与传统方法相比,DFT增强模型显示出具有竞争力或优异的性能.
结论:
- 将DFT计算与机器学习相结合,为预测有机合成中的enantioselectivity提供了一个可行的策略.
- 这种方法克服了计算化学中小型数据集的局限性.
- 该方法为设计选择性化学转换提供了一个强大的工具.
相关概念视频
02:15SN1 Reaction: Stereochemistry
8.6K
This lesson provides an in-depth discussion of the stereochemical outcomes in an SN1 reaction.
In the first step of an SN1 reaction, the bond between the electrophilic carbon and the leaving group ionizes to generate the carbocation intermediate. The second step of the mechanism is the nucleophilic attack.
In the formed carbocation, the positively charged carbon is sp2 hybridized with a trigonal planar geometry. As all the three substituents lie on the same plane, a plane of symmetry for the...
In the first step of an SN1 reaction, the bond between the electrophilic carbon and the leaving group ionizes to generate the carbocation intermediate. The second step of the mechanism is the nucleophilic attack.
In the formed carbocation, the positively charged carbon is sp2 hybridized with a trigonal planar geometry. As all the three substituents lie on the same plane, a plane of symmetry for the...
8.6K
02:23SN2 Reaction: Stereochemistry
9.7K
In an SN2 reaction, the nucleophilic attack on the substrate and departure of the leaving group occurs simultaneously through a transition state. As the nucleophile approaches the substrate from the back-side, the configuration of the substrate carbon changes from tetrahedral to trigonal bipyramidal and then back to tetrahedral, leading to an inversion in the configuration of the product.
If the substrate is an achiral molecule at the α-carbon, the inversion of configuration is not...
If the substrate is an achiral molecule at the α-carbon, the inversion of configuration is not...
9.7K
02:24Predicting Reaction Outcomes
8.5K
Kinetics describes the rate and path by which a reaction occurs. In contrast, thermodynamics deals with state functions and describes the properties, behavior, and components of a system. It is not concerned with the path taken by the process and cannot address the rate at which a reaction occurs. Although it does provide information about what can happen during a reaction process, it does not describe the detailed steps of what appears on an atomic or a molecular level. On the other hand,...
8.5K
02:17Reduction of Alkenes: Asymmetric Catalytic Hydrogenation
3.3K
Catalytic hydrogenation of alkenes is a transition-metal catalyzed reduction of the double bond using molecular hydrogen to give alkanes. The mode of hydrogen addition follows syn stereochemistry.
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
3.3K
02:27Predicting Products: SN1 vs. SN2
13.5K
Nucleophilic substitution reactions of alkyl halides can proceed via an SN1 or an SN2 mechanism. While in SN2 reactions, the nucleophile attacks the substrate simultaneously as the leaving group departs, in SN1 reactions, the substrate first dissociates to give the carbocation intermediate. Various factors such as the structure of the substrate, the strength of the nucleophile, and the nature of the solvent promote one mechanism over the other.
With increased substitution on the alkyl halide,...
With increased substitution on the alkyl halide,...
13.5K
01:26Synthesis of α-Substituted Carbonyl Compounds: The Stork Enamine Reaction
3.4K
α-Substituted ketones or aldehydes can be synthesized from enamines by the Stork enamine reaction, named after its pioneer Gilbert Stork. Enamines are useful synthetic intermediates where the lone pair on nitrogen is in conjugation with the C=C bond. They resemble enolate ions, as the resonance forms of both species have a nucleophilic α carbon.
3.4K