{"title":"Navigating Ultralarge Virtual Chemical Spaces with Product-of-Experts Chemical Language Models","authors":"Shuya Nakata, Yoshiharu Mori, Shigenori Tanaka","doi":"10.1021/acs.jcim.4c01214","DOIUrl":null,"url":null,"abstract":"Ultralarge virtual chemical spaces have emerged as a valuable resource for drug discovery, providing access to billions of make-on-demand compounds with high synthetic success rates. Chemical language models can potentially accelerate the exploration of these vast spaces through direct compound generation. However, existing models are not designed to navigate specific virtual chemical spaces and often overlook synthetic accessibility. To address this gap, we introduce product-of-experts (PoE) chemical language models, a modular and scalable approach to navigating ultralarge virtual chemical spaces. This method allows for controlled compound generation within a desired chemical space by combining a <i>prior</i> model pretrained on the target space with <i>expert</i> and <i>anti-expert</i> models fine-tuned using external property-specific data sets. We demonstrate that the PoE chemical language model can generate compounds with desirable properties, such as those that favorably dock to dopamine receptor D2 (DRD2) and are predicted to cross the blood–brain barrier (BBB), while ensuring that the majority of generated compounds are present within the target chemical space. Our results highlight the potential of chemical language models for navigating ultralarge virtual chemical spaces, and we anticipate that this study will motivate further research in this direction. The source code and data are freely available at https://github.com/shuyana/poeclm.","PeriodicalId":44,"journal":{"name":"Journal of Chemical Information and Modeling ","volume":null,"pages":null},"PeriodicalIF":5.6000,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Chemical Information and Modeling ","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1021/acs.jcim.4c01214","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Ultralarge virtual chemical spaces have emerged as a valuable resource for drug discovery, providing access to billions of make-on-demand compounds with high synthetic success rates. Chemical language models can potentially accelerate the exploration of these vast spaces through direct compound generation. However, existing models are not designed to navigate specific virtual chemical spaces and often overlook synthetic accessibility. To address this gap, we introduce product-of-experts (PoE) chemical language models, a modular and scalable approach to navigating ultralarge virtual chemical spaces. This method allows for controlled compound generation within a desired chemical space by combining a prior model pretrained on the target space with expert and anti-expert models fine-tuned using external property-specific data sets. We demonstrate that the PoE chemical language model can generate compounds with desirable properties, such as those that favorably dock to dopamine receptor D2 (DRD2) and are predicted to cross the blood–brain barrier (BBB), while ensuring that the majority of generated compounds are present within the target chemical space. Our results highlight the potential of chemical language models for navigating ultralarge virtual chemical spaces, and we anticipate that this study will motivate further research in this direction. The source code and data are freely available at https://github.com/shuyana/poeclm.
期刊介绍:
The Journal of Chemical Information and Modeling publishes papers reporting new methodology and/or important applications in the fields of chemical informatics and molecular modeling. Specific topics include the representation and computer-based searching of chemical databases, molecular modeling, computer-aided molecular design of new materials, catalysts, or ligands, development of new computational methods or efficient algorithms for chemical software, and biopharmaceutical chemistry including analyses of biological activity and other issues related to drug discovery.
Astute chemists, computer scientists, and information specialists look to this monthly’s insightful research studies, programming innovations, and software reviews to keep current with advances in this integral, multidisciplinary field.
As a subscriber you’ll stay abreast of database search systems, use of graph theory in chemical problems, substructure search systems, pattern recognition and clustering, analysis of chemical and physical data, molecular modeling, graphics and natural language interfaces, bibliometric and citation analysis, and synthesis design and reactions databases.