Chemical Language Models for Natural Products: A State-Space Model Approach
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arXiv
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| Auteurs principaux: | , , , |
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| Format: | Preprint |
| Publié: |
2026
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| _version_ | 1866915799481974784 |
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| author | Wang, Ho-Hsuan Sultan, Afnan Volkamer, Andrea Klakow, Dietrich |
| author_facet | Wang, Ho-Hsuan Sultan, Afnan Volkamer, Andrea Klakow, Dietrich |
| contents | Language models are widely used in chemistry for molecular property prediction and small-molecule generation, yet Natural Products (NPs) remain underexplored despite their importance in drug discovery. To address this gap, we develop NP-specific chemical language models (NPCLMs) by pre-training state-space models (Mamba and Mamba-2) and comparing them with transformer baselines (GPT). Using a dataset of about 1M NPs, we present the first systematic comparison of selective state-space models and transformers for NP-focused tasks, together with eight tokenization strategies including character-level, Atom-in-SMILES (AIS), byte-pair encoding (BPE), and NP-specific BPE. We evaluate molecule generation (validity, uniqueness, novelty) and property prediction (membrane permeability, taste, anti-cancer activity) using MCC and AUC-ROC. Mamba generates 1-2 percent more valid and unique molecules than Mamba-2 and GPT, with fewer long-range dependency errors, while GPT yields slightly more novel structures. For property prediction, Mamba variants outperform GPT by 0.02-0.04 MCC under random splits, while scaffold splits show comparable performance. Results demonstrate that domain-specific pre-training on about 1M NPs can match models trained on datasets over 100 times larger. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2602_13958 |
| institution | arXiv |
| publishDate | 2026 |
| record_format | arxiv |
| spellingShingle | Chemical Language Models for Natural Products: A State-Space Model Approach Wang, Ho-Hsuan Sultan, Afnan Volkamer, Andrea Klakow, Dietrich Machine Learning Artificial Intelligence Language models are widely used in chemistry for molecular property prediction and small-molecule generation, yet Natural Products (NPs) remain underexplored despite their importance in drug discovery. To address this gap, we develop NP-specific chemical language models (NPCLMs) by pre-training state-space models (Mamba and Mamba-2) and comparing them with transformer baselines (GPT). Using a dataset of about 1M NPs, we present the first systematic comparison of selective state-space models and transformers for NP-focused tasks, together with eight tokenization strategies including character-level, Atom-in-SMILES (AIS), byte-pair encoding (BPE), and NP-specific BPE. We evaluate molecule generation (validity, uniqueness, novelty) and property prediction (membrane permeability, taste, anti-cancer activity) using MCC and AUC-ROC. Mamba generates 1-2 percent more valid and unique molecules than Mamba-2 and GPT, with fewer long-range dependency errors, while GPT yields slightly more novel structures. For property prediction, Mamba variants outperform GPT by 0.02-0.04 MCC under random splits, while scaffold splits show comparable performance. Results demonstrate that domain-specific pre-training on about 1M NPs can match models trained on datasets over 100 times larger. |
| title | Chemical Language Models for Natural Products: A State-Space Model Approach |
| topic | Machine Learning Artificial Intelligence |
| url | https://arxiv.org/abs/2602.13958 |