摩尔价格:基于市场价值评估分子的合成可及性

IF 5.7 2区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Friedrich Hastedt, Klaus Hellgardt, Sophia Yaliraki, Dongda Zhang, Antonio del Rio Chanona
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引用次数: 0

摘要

用于概念化和设计硅化合物的机器学习方法引起了人们的极大关注。然而,这些化合物的适用性经常受到合成可行性和成本效益的挑战。研究人员引入了代理评分,即合成可及性评分,来量化虚拟分子合成的难易程度。尽管它们很实用,但现有的合成可及性工具有明显的局限性:它们忽略了化合物的可购买性,缺乏物理可解释性,并且经常依赖于不完善的计算机辅助合成规划算法。我们介绍了MolPrice,一个准确、快速的分子价格预测模型。MolPrice利用自监督对比学习,自主生成合成复杂分子的价格标签,使模型能够泛化到训练分布之外的分子。我们的研究结果表明,MolPrice可靠地为合成复杂分子分配了比容易购买的分子更高的价格,有效地区分了不同的合成可及性水平。此外,MolPrice在合成可及性的文献基准上取得了具有竞争力的表现。为了证明其实用性,我们进行了一个虚拟筛选案例研究,说明MolPrice如何成功地从大型候选库中识别可购买的分子。MolPrice通过将成本意识整合到合成可及性评估中,弥合了生成分子设计与现实世界可行性之间的差距,使其成为加速分子发现的强大模型。我们介绍了MolPrice,这是一个机器学习模型,可以预测分子价格作为合成可及性的代理。与现有的方法不同,MolPrice将成本意识整合到可获得性评估中,使其能够区分容易购买的分子和合成复杂的分子。该模型计算效率高,适用于大规模虚拟筛选。因此,这项工作提供了一个实用的工具,在早期发现工作流程中优先考虑廉价和合成可行的化合物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
MolPrice: assessing synthetic accessibility of molecules based on market value

Machine learning approaches for conceptualizing and designing in silico compounds have attracted significant attention. However, the applicability of these compounds is often challenged by synthetic viability and cost-effectiveness. Researchers introduced proxy-scores, known as synthethic accessiblity scoring, to quantify the ease of synthesis for virtual molecules. Despite their utility, existing synthetic accessibility tools have notable limitations: they overlook compound purchasability, lack physical interpretability, and often rely on imperfect computer-aided synthesis planning algorithms. We introduce MolPrice, an accurate and fast model for molecular price prediction. Utilizing self-supervised contrastive learning, MolPrice autonomously generates price labels for synthetically complex molecules, enabling the model to generalize to molecules beyond the training distribution. Our results show that MolPrice reliably assigns higher prices to synthetically complex molecules than to readily purchasable ones, effectively distinguishing different levels of synthetic accessibility. Furthermore, MolPrice achieves competitive performance on literature benchmarks for synthetic accessibility. To demonstrate its practical utility, we conduct a virtual screening case study, illustrating how MolPrice successfully identifies purchasable molecules from a large candidate library. MolPrice bridges the gap between generative molecular design and real-world feasibility by integrating cost-awareness into synthetic accessibility assessment, making it a powerful model to accelerate molecular discovery.

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来源期刊
Journal of Cheminformatics
Journal of Cheminformatics CHEMISTRY, MULTIDISCIPLINARY-COMPUTER SCIENCE, INFORMATION SYSTEMS
CiteScore
14.10
自引率
7.00%
发文量
82
审稿时长
3 months
期刊介绍: Journal of Cheminformatics is an open access journal publishing original peer-reviewed research in all aspects of cheminformatics and molecular modelling. Coverage includes, but is not limited to: chemical information systems, software and databases, and molecular modelling, chemical structure representations and their use in structure, substructure, and similarity searching of chemical substance and chemical reaction databases, computer and molecular graphics, computer-aided molecular design, expert systems, QSAR, and data mining techniques.
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