Friedrich Hastedt, Klaus Hellgardt, Sophia Yaliraki, Dongda Zhang, Antonio del Rio Chanona
{"title":"摩尔价格:基于市场价值评估分子的合成可及性","authors":"Friedrich Hastedt, Klaus Hellgardt, Sophia Yaliraki, Dongda Zhang, Antonio del Rio Chanona","doi":"10.1186/s13321-025-01076-3","DOIUrl":null,"url":null,"abstract":"<div><p>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 <i>MolPrice</i>, an accurate and fast model for molecular price prediction. Utilizing self-supervised contrastive learning, <i>MolPrice</i> autonomously generates price labels for synthetically complex molecules, enabling the model to generalize to molecules beyond the training distribution. Our results show that <i>MolPrice</i> reliably assigns higher prices to synthetically complex molecules than to readily purchasable ones, effectively distinguishing different levels of synthetic accessibility. Furthermore, <i>MolPrice</i> achieves competitive performance on literature benchmarks for synthetic accessibility. To demonstrate its practical utility, we conduct a virtual screening case study, illustrating how <i>MolPrice</i> successfully identifies purchasable molecules from a large candidate library. <i>MolPrice</i> 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.</p></div>","PeriodicalId":617,"journal":{"name":"Journal of Cheminformatics","volume":"17 1","pages":""},"PeriodicalIF":5.7000,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://jcheminf.biomedcentral.com/counter/pdf/10.1186/s13321-025-01076-3","citationCount":"0","resultStr":"{\"title\":\"MolPrice: assessing synthetic accessibility of molecules based on market value\",\"authors\":\"Friedrich Hastedt, Klaus Hellgardt, Sophia Yaliraki, Dongda Zhang, Antonio del Rio Chanona\",\"doi\":\"10.1186/s13321-025-01076-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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 <i>MolPrice</i>, an accurate and fast model for molecular price prediction. Utilizing self-supervised contrastive learning, <i>MolPrice</i> autonomously generates price labels for synthetically complex molecules, enabling the model to generalize to molecules beyond the training distribution. Our results show that <i>MolPrice</i> reliably assigns higher prices to synthetically complex molecules than to readily purchasable ones, effectively distinguishing different levels of synthetic accessibility. Furthermore, <i>MolPrice</i> achieves competitive performance on literature benchmarks for synthetic accessibility. To demonstrate its practical utility, we conduct a virtual screening case study, illustrating how <i>MolPrice</i> successfully identifies purchasable molecules from a large candidate library. <i>MolPrice</i> 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.</p></div>\",\"PeriodicalId\":617,\"journal\":{\"name\":\"Journal of Cheminformatics\",\"volume\":\"17 1\",\"pages\":\"\"},\"PeriodicalIF\":5.7000,\"publicationDate\":\"2025-09-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://jcheminf.biomedcentral.com/counter/pdf/10.1186/s13321-025-01076-3\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Cheminformatics\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://link.springer.com/article/10.1186/s13321-025-01076-3\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Cheminformatics","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1186/s13321-025-01076-3","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
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.
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.