AI-assisted protein design has emerged as a critical tool for advancing biotechnology, as deep generative models have demonstrated their reliability in this domain. However, most existing models primarily utilize protein sequence or structural data for training, neglecting the physicochemical properties of proteins.Moreover, they are deficient to control the generation of proteins in intuitive conditions. To address these limitations,we propose CMADiff here, a novel framework that enables controllable protein generation by aligning the physicochemical properties of protein sequences with text-based descriptions through a latent diffusion process. Specifically, CMADiff employs a Conditional Variational Autoencoder (CVAE) to integrate physicochemical features as conditional input, forming a robust latent space that captures biological traits. In this latent space, we apply a conditional diffusion process, which is guided by BioAligner, a contrastive learning-based module that aligns text descriptions with protein features, enabling text-driven control over protein sequence generation. Validated by a series of evaluations including AlphaFold3, the experimental results indicate that CMADiff outperforms protein sequence generation benchmarks and holds strong potential for future applications. The implementation and code are available at https://github.com/HPC-NEAU/PhysChemDiff.
Zhen Yang, Ping Jian Beijing Institute of Technology, Zhongbin Guo, Zuming Zhang Nanyang Technological University, Chengzhi Li Beijing Institute of Technology, Yonghong Deng Beijing Institute of Technology, Xinyue Zhang, Wenpeng Lu
Over the past year, spatial intelligence has drawn increasing attention. Many prior works study it from the perspective of visual-spatial intelligence, where models have access to visuospatial information from visual inputs. However, in the absence of visual information, whether linguistic intelligence alone is sufficient to endow models with spatial intelligence, and how models perform relevant tasks with text-only inputs still remain unexplored. Therefore, in this paper, we focus on a fundamental and critical capability in spatial intelligence from a linguistic perspective: viewpoint rotation understanding (VRU). Specifically, LLMs and VLMs are asked to infer their final viewpoint and predict the corresponding observation in an environment given textual description of viewpoint rotation and observation over multiple steps. We find that both LLMs and VLMs perform poorly on our proposed dataset while human can easily achieve 100% accuracy, indicating a substantial gap between current model capabilities and the requirements of spatial intelligence. To uncover the underlying mechanisms, we conduct a layer-wise probing analysis and head-wise causal intervention. Our findings reveal that although models encode viewpoint information in the hidden states, they appear to struggle to bind the viewpoint position with corresponding observation, resulting in a hallucination in final layers. Finally, we selectively fine-tune the key attention heads identified by causal intervention to improve VRU performance. Experimental results demonstrate that such selective fine-tuning achieves improved VRU performance while avoiding catastrophic forgetting of generic abilities.
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Proceedings of the 64th Annual Meeting of the Association for Computational Linguistics (Volume 1: Long Papers) · 2026 · 正式发表