Protein language models (PLMs) have emerged as powerful tools for controllable biomolecular design, yet their post-training adaptation typically relies on costly wet-lab validation or curated preference datasets. To overcome this supervision bottleneck, we introduce unsupervised reward optimization of PLMs, a comprehensive framework for steerable protein generation without ground-truth labels.
arXiv:2607. 02834v1 Announce Type: new Abstract: Molecular optimization often starts from a pretrained generative model that captures a broad prior over valid molecular structures.
By Trevor Chen, Ariel Dai, Jason Yang, Riccardo De Santi, Daniel Khalil, Wenda Chu, Nate Gruver, Pranav Murugan, Alexander F. G. Goldberg, Maruan Al-Shedivat, Yisong Yue
arXiv:2607. 19044v1 Announce Type: new Abstract: Leveraging large language models (LLMs) for molecular generation has shown remarkable potential in chemical and drug design.
By Mingxuan Ouyang, Hao Lan, Wanyu Lin
arXiv:2608. 15669v1 Announce Type: new Abstract: Scientific discovery often involves optimising expensive-to-evaluate objectives over vast, structured, and open-ended hypothesis spaces, such as molecules, protein sequences, and computer programs.
By Zhongwei Yu, Yan Song, Xue Yan, Anjie Liu, Xingyu Lu, Yihang Chen, Huichi Zhou, Siyuan Guo, Luoyang Sun, Sihan Chen, Xiangning Yu, Jun Wang
arXiv:2607. 26391v1 Announce Type: new Abstract: Oracle-limited molecular optimization gives reward only after a complete molecule is generated, while each rollout requires many local next-token decisions.
By Xinyu Wang, Jinbo Bi, Minghu Song
Oracle-limited molecular optimization gives reward only after a complete molecule is generated, while each rollout requires many local next-token decisions. This delayed-feedback interface makes molecular policy optimization myopic: an optimizer can learn that a molecule was good without knowing which intermediate actions made it good.
arXiv:2606. 24990v1 Announce Type: new Abstract: Reinforcement Learning (RL) has become a powerful paradigm for de novo molecular design, enabling Chemical Language Models (CLMs) to navigate and explore the chemical space while optimizing specific desired properties.
By Borja Medina, Jon Paul Janet
arXiv:2503. 00539v2 Announce Type: replace-cross Abstract: Reinforcement learning from human feedback (RLHF) has evolved to be one of the main methods for fine-tuning large language models (LLMs).
By Debmalya Mandal, Paulius Sasnauskas, Goran Radanovic
arXiv:2605. 15354v2 Announce Type: replace Abstract: Despite the success of foundation models in language and vision, molecular graph generation still lacks a unified framework for heterogeneous design tasks with reliable controllability.
By Yihan Zhu, Yuhan Liu, Weijiang Li, Tengfei Luo, Meng Jiang
arXiv:2606. 02386v1 Announce Type: new Abstract: Protein language models (PLMs) are passive oracles: they generate sequences in a single forward pass with no mechanism to consult external biophysical feedback or redirect generation when a candidate violates thermodynamic or structural constraints.
By Sahil Rahman, Maxx Richard Rahman
arXiv:2606. 27939v1 Announce Type: cross Abstract: Protein language models are standard priors for biological sequence generation, but steering them toward explicit distributional design targets remains largely unexplored.
By Violeta Basten-Romero, Rub\'en Mu\~noz-Tafalla, Anna Mar\'ia D\'iaz-Rovira, Bertran Miquel-Oliver, Isaac Filella-Merce, V\'ictor Guallar
arXiv:2607. 06987v1 Announce Type: new Abstract: Reinforcement learning (RL) has become the standard paradigm for enhancing the complex reasoning capabilities of large language models (LLMs).
By Chongyu Fan, Pengfei Liu, Jingjia Huang, Sijia Liu, Yi Lin