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arXiv · 2503.06687

UniGenX: a unified generative foundation model that couples sequence, structure and function to accelerate scientific design across proteins, molecules and materials

Gongbo Zhang·Yanting Li·Renqian Luo·Pipi Hu·Yang Yang·Zeru Zhao·Lingbo Li·Guoqing Liu·Zun Wang·Ran Bi·Kaiyuan Gao·Liya Guo·Yu Xie·Chang Liu·Jia Zhang·Tian Xie·Robert Pinsler·Claudio Zeni·Ziheng Lu·Hongxia Hao·Yingce Xia·Marwin Segler·Maik Riechert·Wei Yang·Hao Jiang·Wen-Bin Zhang·Zhijun Zeng·Yi Zhu·Li Dong·Xiuyuan Hu·Li Yuan·Lei Chen·Haiguang Liu·Tao Qin
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Abstract

Function in natural systems arises from one-dimensional sequences forming three-dimensional structures with specific properties. However, current generative models suffer from critical limitations: training objectives seldom target function directly, discrete sequences and continuous coordinates are optimized in isolation, and conformational ensembles are under-modeled. We present UniGenX, a unified generative foundation model that addresses these gaps by co-generating sequences and coordinates under direct functional and property objectives across proteins, molecules, and materials. UniGenX represents heterogeneous inputs as a mixed stream of symbolic and numeric tokens, where a decoder-only autoregressive transformer provides global context and a conditional diffusion head generates numeric fields steered by task-specific tokens. Besides the new high SOTAs on structure prediction tasks, the model demonstrates state-of-the-art or competitive performance for the function-aware generation across domains: in materials, it achieves "conflicted" multi-property conditional generation, yielding 436 crystal candidates meeting triple constraints, including 11 with novel compositions; in chemistry, it sets new benchmarks on five property targets and conformer ensemble generation on GEOM; and in biology, it improves success in modeling protein induced fit (RMSD < 2 Å) by over 23-fold and enhances EC-conditioned enzyme design. Ablation studies and cross-domain transfer substantiate the benefits of joint discrete-continuous training, establishing UniGenX as a significant advance from prediction to controllable, function-aware generation.

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Gongbo Zhang, Yanting Li, Renqian Luo, Pipi Hu, Yang Yang, Zeru Zhao, Lingbo Li, Guoqing Liu, Zun Wang, Ran Bi, Kaiyuan Gao, Liya Guo, Yu Xie, Chang Liu, Jia Zhang, Tian Xie, Robert Pinsler, Claudio Zeni, Ziheng Lu, Hongxia Hao, Yingce Xia, Marwin Segler, Maik Riechert, Wei Yang, Hao Jiang, Wen-Bin Zhang, Zhijun Zeng, Yi Zhu, Li Dong, Xiuyuan Hu, Li Yuan, Lei Chen, Haiguang Liu, Tao Qin. 2025-08-26. UniGenX: a unified generative foundation model that couples sequence, structure and function to accelerate scientific design across proteins, molecules and materials. https://arxiv.org/abs/2503.06687

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