Stereochemistry-aware string-based molecular generation
This study investigates the impact of incorporating stereochemical information, a crucial aspect of computational drug discovery and materials design, in molecular generative modeling. We present a detailed comparison of stereochemistry-aware and conventionally stereochemistry-unaware string-based generative approaches, utilizing both genetic algorithms and reinforcement learning-based techniques. To evaluate these models, we introduce novel benchmarks specifically designed to assess the importance of stereochemistry-aware generative modeling. Our results demonstrate that stereochemistry-aware models generally perform on par with or surpass conventional algorithms across various stereochemistry-sensitive tasks. However, we also observe that in scenarios where stereochemistry plays a less critical role, stereochemistry-aware models may face challenges due to the increased complexity of the chemical space they must navigate. This work provides insights into the trade-offs involved in incorporating stereochemical information in molecular generative models and offers guidance for selecting appropriate approaches based on specific application requirements.
Authors
- Naruki Yoshikawa (ORCID: https://orcid.org/0000-0003-1546-8709)
- Edwin Yu
- Alán Aspuru‐Guzik (ORCID: https://orcid.org/0000-0002-8277-4434)
- Gary Tom (ORCID: https://orcid.org/0000-0002-8470-6515)
- Kjell Jorner (ORCID: https://orcid.org/0000-0002-4191-6790)
Institutions
- Canadian Institute for Advanced Research (CA)
- University of Toronto (CA)
- ETH Zurich (CH)
- Vector Institute (CA)
- Chalmers University of Technology (SE)
Publication Details
- Journal
- PNAS Nexus
- Published
- 2025-10-14
- DOI
- https://doi.org/10.1093/pnasnexus/pgaf329
- Citations
- 1
- Primary Topic
- Various Chemistry Research Topics
- Type
- article
- Field-Weighted Citation Impact
- 1.75
Funders
- Canadian Institute for Advanced Research
- Ministère de l'Économie, de la Science et de l'Innovation - Québec
- Vetenskapsrådet
- Alliance de recherche numérique du Canada
- Natural Sciences and Engineering Research Council of Canada