Fang Wu, Hongbin Lin, Bingchen Duan, Yuchen Wang, Li Erran Li, Yanjie Huang, Mingxuan Cao, Yijun Ma 等 27 位作者
Protein-protein interactions underpin nearly all biological processes. Yet, designing proteins with desired interactions remains challenging due to the structural complexity governing molecular recognition. This study views protein design as a search optimization problem over a combinatorial sequence space under expensive structural evaluation. Toward this goal, we introduce a novel tree-based search framework, ProteoCraft, that employs approximate structural gradients from diffusion-based structure predictors as effective proposal policies to specify where the search should explore. Complete no-gradient inference of folding models separately assigns values to the resulting sequences, determining what is good. ProteoCraft allocates this verification budget through a coarse-to-fine paradigm: multi-site edits first explore distinct sequence basins, then verified promising states undergo strict single-site refinement. Across fourteen de novo binder-design settings spanning eight target proteins, five immune-relevant TCR-facing targets, and four localized CDR redesign tasks, ProteoCraft improves design quality and high-confidence yield. These improvements persist under independent AF2-IG and Rosetta-based interface evaluation. Prospective experimental validation further yielded an 82.9% binding hit rate for PD-L1 miniproteins, with a best measured KD of 0.879 nM, and confirmed binding of designed IFNAR2 VHH. Our code is available at https://github.com/smiles724/ProteoCraft_v1.
Xinyue Xu, Hongbin Lin, Juangui Xu, Hualiang Wang, Lehan Wang, Lijie Hu, Adrian Weller, Xiaomeng Li
Medical imaging modalities such as ultrasound and X-ray are widely used in clinical practice, where diagnosis follows a structured, evidence-driven workflow aligned with standardized criteria. While multimodal large language models (MLLMs) show promise for automated medical report generation, most existing systems rely on end-to-end multimodal fusion without modeling clinically defined intermediate attributes, leading to limited grounding and interpretability. To address this issue, we propose CORAL (COncept-grounded ReAsoning with Localization), a multimodal framework that integrates spatial grounding and concept-level supervision into a unified reasoning process. CORAL employs a prompt-driven medical segmentation model to localize lesions and predicts multi-class clinical attributes through a Concept Bottleneck module. The resulting textual concept tokens are combined with mask-modulated visual features within an MLLM to enable structured report generation and diagnostic prediction. Experiments on BUS-CoT and IU X-ray datasets demonstrate consistent improvements in diagnostic accuracy, concept consistency, and report quality over strong general-purpose and medical MLLMs, indicating that concept-grounded reasoning better aligns generation with clinical decision processes.