Domain-Agnostic Molecular Generation with Self-feedback

The generation of molecules with desired properties has gained tremendous popularity, revolutionizing the way scientists design molecular structures and providing valuable support for chemical and drug design. However, despite the potential of language models in molecule generation, they face numerous challenges such as the generation of syntactically or chemically flawed molecules, narrow domain focus, and limitations in creating diverse and directionally feasible molecules due to a dearth of annotated data or external molecular databases. To tackle these challenges, we introduce MolGen, a pre-trained molecular language model tailored specifically for molecule generation. Through the reconstruction of over 100 million molecular SELFIES, MolGen internalizes profound structural and grammatical insights. This is further enhanced by domain-agnostic molecular prefix tuning, fostering robust knowledge transfer across diverse domains. Importantly, our self-feedback paradigm steers the model away from ``molecular hallucinations'', ensuring alignment between the model's estimated probabilities and real-world chemical preferences. Extensive experiments on well-known benchmarks underscore MolGen's optimization capabilities in properties such as penalized logP, QED, and molecular docking. Additional analyses affirm its proficiency in accurately capturing molecule distributions, discerning intricate structural patterns, and efficiently exploring the chemical space. Code is available at https://github.com/zjunlp/MolGen.