Maojiang Su, Jiale Chen, Qijie Zhu, Shang Wu, Jiayi Wang, Jihai Zhao, Guo Ye, Yibo Wen 等 9 位作者
PairFormer-based all-atom models demonstrate strong capabilities in biomolecular binder design. However, existing methods often use all-atom representations for modality-specific binder design, such as protein and peptide design. In contrast, recent geometric latent diffusion models pursue unified binder design by representing molecular blocks from different modalities in a shared latent space. These complementary strengths motivate us to investigate how to generalize the use of pretrained all-atom representations to unified binder design. We introduce PairFuse, a parameter-efficient method that enables this generalization through representation fusion. Specifically, we use lightweight layerwise adapters to integrate pretrained all-atom representations into an independently pretrained geometric latent diffusion model. Our adapters integrate pretrained all-atom representations through two mechanisms: enriching the diffusion model's molecular block features and incorporating pairwise structural information into the geometric diffusion model's denoiser. Theoretically, we prove that the augmented denoiser preserves geometry and pairwise attention fusion provides additional attention expressivity beyond feature-only fusion. Experimentally, across antibody, peptide, and small molecule binder-design benchmarks, PairFuse achieves stronger performance than the pretrained diffusion model and existing representation-fusion baselines.
Ziqing Wang, Yibo Wen, Abhishek Pandey, Han Liu Northwestern University, Kaize Ding Northwestern University
In drug discovery, molecular optimization aims to iteratively refine a lead compound to improve molecular properties while preserving structural similarity to the original molecule. However, each oracle evaluation is expensive, making sample efficiency a key challenge for existing methods under a limited oracle budget. Trial-and-error approaches require many oracle calls, while methods that leverage external knowledge tend to reuse familiar templates and struggle on challenging objectives. A key missing piece is long-term memory that can ground decisions and provide reusable insights for future optimizations. To address this, we present MolMem (Molecular optimization with Memory), a multi-turn agentic reinforcement learning (RL) framework with a dual-memory system. Specifically, MolMem uses Static Exemplar Memory to retrieve relevant exemplars for cold-start grounding, and Evolving Skill Memory to distill successful trajectories into reusable strategies. Built on this memory-augmented formulation, we train the policy with dense step-wise rewards, turning costly rollouts into long-term knowledge that improves future optimization. Extensive experiments show that MolMem achieves 90% success on single-property tasks (1.5\times over the best baseline) and 52% on multi-property tasks using only 500 oracle calls. Our code is available at https://github.com/REAL-Lab-NU/MolMem.
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cs.CL · cs.AI
Proceedings of the 64th Annual Meeting of the Association for Computational Linguistics (Volume 1: Long Papers) · 2026 · 正式发表
Ziqing Wang, Kexin Zhang, Zihan Zhao, Yibo Wen, Abhishek Pandey, Han Liu Northwestern University, Kaize Ding Northwestern University
Large language models (LLMs) are introducing a paradigm shift in molecular discovery by enabling text-guided interaction with chemical spaces through natural language and symbolic notations, with emerging extensions to incorporate multi-modal inputs. To advance this emerging field, this survey provides an up-to-date and forward-looking review of the emerging use of LLMs for two central tasks: molecule generation and molecule optimization. We organize our survey around four fundamental challenges that have emerged as critical evaluation dimensions in recent studies: ensuring validity, enhancing synthesizability, achieving precise property control, and maximizing diversity. Based on this, we systematically analyze how current LLM learning paradigms are applied to tackle each challenge, revealing the distinct capabilities and inherent limitations of each approach. In addition, we include the commonly used datasets and evaluation protocols aligned with these challenges. We conclude by discussing future directions, positioning this survey as a resource for researchers working at the intersection of LLMs and molecular science. A continuously updated reading list is available at https://github.com/REAL-Lab-NU/Awesome-LLM-Centric-Molecular-Discovery.
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cs.CL
Proceedings of the 64th Annual Meeting of the Association for Computational Linguistics (Volume 1: Long Papers) · 2026 · 正式发表