Folding-Based End-To-End Chemical Drug Design with Uncertainty Estimation: Tackling Hallucination in the Post-GPT Era
In the post-GPT era, Llama-Gram represents a promising advancement in AI-driven chemical drug discovery, grounded in the chemical principle that molecular structure determines properties. This folding-based end-to-end framework seeks to address the hallucination issues of traditional large language models by integrating protein folding embeddings, graph-based molecular representations, and uncertainty estimation to better capture the structural complexities of protein-ligand interactions. By leveraging the frozen-gradient ESMFold model and a Graph Transformer variant, Llama-Gram aims to enhance predictive accuracy and reliability through grouped-query attention and a Gram layer inspired by support points theory. By incorporating protein folding information, the model demonstrates competitive performance against state-of-the-art approaches such as Transformer CPI 2.0 and Graph-DTA, offering improvements in compound-target interaction. Llama-Gram provides a scalable and innovative chemical theory that could contribute to accelerating the chemical drug discovery process.
Authors
- Schork Ma
- Dingyan Wang (ORCID: https://orcid.org/0000-0003-2964-7425)
- Rongcai Yue (ORCID: https://orcid.org/0000-0001-7908-0928)
- Jin-xing Chen
- Feisheng Zhong
- Shiming Chen (ORCID: https://orcid.org/0000-0002-1216-004X)
Institutions
- Fujian Medical University (CN)
- Target (United States) (US)
- Shanghai Innovative Research Center of Traditional Chinese Medicine (CN)
- Drug Discovery Laboratory (Norway) (NO)
Publication Details
- Journal
- Journal of Medicinal Chemistry
- Published
- 2025-03-08
- DOI
- https://doi.org/10.1021/acs.jmedchem.5c00271
- Citations
- 3
- Primary Topic
- Computational Drug Discovery Methods
- Type
- article
- Field-Weighted Citation Impact
- 4.51
Funders
- Department of Education, Fujian Province
- Fujian Medical University