Scientific databases aggregate vast amounts of quantitative data alongside descriptive text. In biochemistry, chemical screening assays evaluate the functional responses of candidate compounds against disease targets. Unstructured text that describes the biological mechanisms through which these targets operate, experimental screening protocols, and other attributes of assays offer rich information for new drug discovery campaigns, but has been untapped because of that unstructured format. We present Assay2Mol, a large language model-based workflow that can capitalize on the vast existing biochemical screening assays for early-stage drug discovery. Assay2Mol retrieves existing assay records involving targets similar to the new target and generates candidate compounds using in-context learning with the retrieved assay screening data. Assay2Mol outperforms recent machine learning approaches that generate candidate ligand compounds for target protein structures, while also promoting more synthesizable molecule generation.

Large Language Models (LLMs) like ChatGPT excel at diverse tasks when given explicit instructions, yet they often struggle with specialized domains such as molecular science, lacking in-depth reasoning and sophisticated planning capabilities. To address these limitations, we introduce ChatMol Copilot, a chatbot-like agent specifically engineered for protein design and small molecule computations. ChatMol Copilot employs a multi-level abstraction framework to expand the LLM‘s capability. At the basic level, it integrates external computational tools through function calls, thus offloading complex tasks and enabling a focus on strategic decision-making. The second level is data abstraction. Large data sets (such as a large number of molecules created by a generative model) are stored in Redis cache, and the redis keys are referenced by LLMs for data sources involved in computation. The third level of abstraction allows the LLM to orchestrate these tools, either directly or via dynamically generated Python executables. Our evaluations demonstrate that ChatMol Copilot can adeptly manage molecular modeling tasks, effectively utilizing a variety of tools as directed. By simplifying access to sophisticated molecular modeling resources, ChatMol Copilot stands to significantly accelerate drug discovery and biotechnological innovation, empowering biochemists with advanced, user-friendly AI capabilities. The open-sourced code is available at https://github.com/ChatMol/ChatMol

Maintaining faithfulness between responses and knowledge is an important research topic for building reliable knowledge-grounded dialogue systems. Existing models heavily rely on elaborate data engineering or increasing the model’s parameters ignoring to track the tokens that significantly influence losses, which is decisive for the optimization direction of the model in each iteration. To address this issue, we propose Focus Learning (FocusL), a novel learning approach that adjusts the contribution of each token to the optimization direction by directly scaling the corresponding objective loss. Specifically, we first introduce a positioning method by utilizing similarity distributions between knowledge and each response token to locate knowledge-aware tokens. Then, we further design a similarity-to-weight transformation to provide dynamic token-level weights for the cross-entropy loss. Finally, we use the weighted loss to encourage the model to pay special attention to the knowledge utilization. Experimental results demonstrate that our method achieves the new state-of-the-art results and generates more reliable responses while maintaining training stability.