Yuxuan Song

Jinyi Hu, Shengding Hu, Yuxuan Song et al. · tsinghua

We present ACDiT, a novel Autoregressive blockwise Conditional Diffusion Transformer, that innovatively combines autoregressive and diffusion paradigms for modeling continuous visual information. By introducing a block-wise autoregressive unit, ACDiT offers a flexible interpolation between token-wise autoregression and full-sequence diffusion, bypassing the limitations of discrete tokenization. The generation of each block is formulated as a conditional diffusion process, conditioned on prior blocks. ACDiT is easy to implement, as simple as creating a Skip-Causal Attention Mask (SCAM) on standard diffusion transformer during training. During inference, the process iterates between diffusion denoising and autoregressive decoding that can make full use of KV-Cache. We show that ACDiT performs best among all autoregressive baselines under similar model scales on image and video generation tasks. We also demonstrate that benefiting from autoregressive modeling, pretrained ACDiT can be transferred in visual understanding tasks despite being trained with the diffusion objective. The analysis of the trade-off between autoregressive modeling and diffusion demonstrates the potential of ACDiT to be used in long-horizon visual generation tasks. We hope that ACDiT offers a novel perspective on visual autoregressive generation and unlocks new avenues for unified models.

Bo Qiang, Wenxian Shi, Yuxuan Song et al.

Proteolysis targeting chimeras (PROTACs) are small molecules that trigger the breakdown of traditionally ``undruggable'' proteins by binding simultaneously to their targets and degradation-associated proteins. A key challenge in their rational design is understanding their structural basis of activity. Due to the lack of crystal structures (18 in the PDB), existing PROTAC docking methods have been forced to simplify the problem into a distance-constrained protein-protein docking task. To address the data issue, we develop a novel pseudo-data generation scheme that requires only binary protein-protein complexes. This new dataset enables PROflow, an iterative refinement model for PROTAC-induced structure prediction that models the full PROTAC flexibility during constrained protein-protein docking. PROflow outperforms the state-of-the-art across docking metrics and runtime. Its inference speed enables the large-scale screening of PROTAC designs, and computed properties of predicted structures achieve statistically significant correlations with published degradation activities.

Bo Qiang, Yuxuan Song, Minkai Xu et al.

Generating desirable molecular structures in 3D is a fundamental problem for drug discovery. Despite the considerable progress we have achieved, existing methods usually generate molecules in atom resolution and ignore intrinsic local structures such as rings, which leads to poor quality in generated structures, especially when generating large molecules. Fragment-based molecule generation is a promising strategy, however, it is nontrivial to be adapted for 3D non-autoregressive generations because of the combinational optimization problems. In this paper, we utilize a coarse-to-fine strategy to tackle this problem, in which a Hierarchical Diffusion-based model (i.e.~HierDiff) is proposed to preserve the validity of local segments without relying on autoregressive modeling. Specifically, HierDiff first generates coarse-grained molecule geometries via an equivariant diffusion process, where each coarse-grained node reflects a fragment in a molecule. Then the coarse-grained nodes are decoded into fine-grained fragments by a message-passing process and a newly designed iterative refined sampling module. Lastly, the fine-grained fragments are then assembled to derive a complete atomic molecular structure. Extensive experiments demonstrate that HierDiff consistently improves the quality of molecule generation over existing methods