Design and Research of a Dual-Target Drug Molecular Generation Model Based on Reinforcement Learning
Dual-target drug design addresses complex diseases and drug resistance, yet existing computational approaches struggle with simultaneous multi-protein optimization. This study presents SFG-Drug, a novel dual-target molecular generation model combining Monte Carlo tree search with gated recurrent unit neural networks for simultaneous MEK1 and mTOR targeting. The methodology employed DigFrag digital fragmentation on ZINC-250k dataset, integrated low-frequency masking techniques for enhanced diversity, and utilized molecular docking scores as reward functions. Comprehensive evaluation on MOSES benchmark demonstrated superior performance compared to state-of-the-art methods, achieving perfect validity (1.000), uniqueness (1.000), and novelty (1.000) scores with highest internal diversity indices (0.878 for IntDiv1, 0.860 for IntDiv2). Over 90% of generated molecules exhibited favorable binding affinity with both targets, showing optimal drug-like properties including QED values in [0.2, 0.7] range and high synthetic accessibility scores. Generated compounds demonstrated structural novelty with Tanimoto coefficients below 0.25 compared to known inhibitors while maintaining dual-target binding capability. The SFG-Drug model successfully bridges the gap between computational prediction and practical drug discovery, offering significant potential for developing new dual-target therapeutic agents and advancing AI-driven pharmaceutical research methodologies.
Authors
- Wei Gao (ORCID: https://orcid.org/0009-0004-6219-1065)
- Dazhou Li (ORCID: https://orcid.org/0000-0002-5072-5611)
- Yuchen Zhou
- Hongyun Li
- Peilin Li
- Ziyan Yan
Institutions
- Quanzhou Normal University (CN)
- Liming Vocational University (CN)
- Shenyang University of Chemical Technology (CN)
Publication Details
- Journal
- Inventions
- Published
- 2026-01-26
- DOI
- https://doi.org/10.3390/inventions11010012
- Primary Topic
- Computational Drug Discovery Methods
- Type
- article
- Field-Weighted Citation Impact
- 0.00