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.
Jiahuan Zhang, Shunwen Bai Zhejiang University, Tianheng Wang Hangzhou Institute of Medicine Chinese Academy of Science, KaiWen Guo Westlake University, Zijia Song National University of Defense Technology, Hanqing WU, Guozheng Rao Tianjin University, Kai Han The University of Hong Kong 等 9 位作者
Humans naturally possess the spatial reasoning ability to form and manipulate images and structures of objects in space. There is an increasing effort to endow Vision-Language Models (VLMs) with similar spatial reasoning capabilities. However, it remains unclear whether these models truly understand and manipulate spatial objects or not. To address this question, we propose a new evaluation framework aimed at assessing the performance of VLMs in spatial deformation reasoning tasks. Specifically, we construct a benchmark for spatial deformation reasoning from 2D to 3D. We explore whether the model can effectively perform spatial deformation reasoning from two directions: forward reasoning (given the operations, find the final state) and reverse reasoning (given the final state, determine the operations). We adopt a ladder competition format, using the number of deformation steps as the level classification criterion, with the goal of exploring the boundaries of the model’s deformation reasoning capabilities. Interestingly, the benchmarking results reveal that almost no model demonstrates plausible spatial deformation reasoning abilities. Furthermore, even after applying targeted training and mainstream reasoning enhancement methods, the models are still unable to perform well on 3D spatial deformation reasoning.
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cs.CL · cs.CV
Proceedings of the 64th Annual Meeting of the Association for Computational Linguistics (Volume 1: Long Papers) · 2026 · 正式发表