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.
Ziqiao Xi, Shuang Liang, Qi Liu University of California, San Diego, Jiaqing Zhang, Letian Peng, Fang Nan University of California, San Diego, Meshal Nayim, Tianhui Zhang University of California, San Diego 等 12 位作者
To close the gap between LLM-based agents and humans in planning and reasoning, agents need large-scale, diverse environments for continuous learning—yet building such environments is itself prohibitively expensive. We present C-World, an environment creation system that enables users to build agent environments on demand. We define a complete agent environment through four components: an Action Space of 5,571 format-unified tools across 204 common applications, a Task Distribution engine that synthesizes long-horizon workflows with wild constraints, a Transition Function implemented as a state controller that injects realistic failures and perturbations, and a Reward Signal combining verifiable metrics with LLM-based judgment. C-World operates in two modes: a realistic mode grounded in live API execution, and a synthesized mode powered by the World Engine, which approximates tool behavior without live service access, enabling scalable environment creation—including environments for domains and tools that do not yet exist in the real world. Evaluation of nine state-of-the-art LLMs reveals that planning ability is uniformly strong but execution remains the bottleneck, and that constraint following—not tool invocation—is the dominant failure mode. The World Engine achieves Spearman \rho = 0.883 ranking correlation with real execution, and fine-tuning on just 1,170 C-World trajectories outperforms baselines trained on 119k samples, demonstrating C-World’s dual value as a rigorous evaluation environment and a scalable data engine. Our code and data are available at https://ziqiao-git.github.io/C-World/.
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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