Discrete structural tokenization provides a promising route to autoregressive 3D molecular generation. Yet, existing tokenizers face a trade-off between compact representation and all-atom reconstruction: atom-level tokens preserve atomic details but produce long sequences, while compact residue-level protein tokens typically omit side-chain geometry. To overcome this limitation, we propose All-atom Diffusion Tokenizer (ADT), which decouples token granularity from reconstruction resolution. ADT uses one structural token per atom for small molecules and one token per protein residue that jointly represents backbone and side-chain geometry. To mitigate geometric distortion introduced by quantization, we leverage the generative capacity of diffusion models to recover fine-grained atomic geometry beyond deterministic decoding from discrete tokens. Extensive experiments across small molecules and proteins demonstrate that ADT achieves strong reconstruction from compact discrete representations while enabling high-quality autoregressive generation of both small molecules and all-atom protein structures. These results establish compact structural tokens as an effective discrete interface for all-atom molecular reconstruction and generation.
Figures & tables
Figure 1: Illustration of tokenizer granularity. (a) Atom-level tokenization assigns one token to each atom. (b) Backbone-only tokenization omits side-chain geometry. (c) ADT jointly encodes backbone and side-chain geometry into one token per residue and reconstructs the all-atom structure.
Figure 2: Overview of ADT. (a) All-atom structures are represented at chemical-unit granularity. (b) Each unit is mapped to a discrete structural token via FSQ. (c) Conditional diffusion reconstructs all-atom geometry, with residue-to-atom expansion for proteins. (d) ADT enables autoregressive generation of all-atom molecular structures.
Type
Method
Match ↑
RMSD ↓
Continuous
GeoLDM ( Xu et al., 2023 )
87.2
0.1820
ADiT ( Joshi et al., 2025 )
94.6
0.0890
SinAE ( Ren et al., 2026 )
100.0
0.0007
Discrete
Mol-StrucTok ( Gao et al., 2026 )
90.7
0.1280
CoordToken Geikyan et al. (2026)
99.4
0.0478
ADT (Ours)
99.7
0.0343
Table 1: Reconstruction results on QM9.
Method
Conformer
Structure
Scaffolds
RMSD ↓
Valid ↑
RMSD ↓
Valid ↑
RMSD ↓
Valid ↑
mol2token ( Liu et al., 2025 )
0.2010
47.1
0.2010
47.1
0.2010
47.1
CoordToken Geikyan et al. (2026)
0.0671
100.0
0.0673
100.0
0.0671
100.0
ADT (Ours)
0.0499
100.0
0.0512
100.0
0.0511
100.0
Table 2: Reconstruction performance on the ∇2 DFT benchmark.
Method
C α -lDDT ↑
BB RMSD ↓
AA lDDT ↑
AA RMSD ↓
TM-score ↑
GDT-TS ↑
GDT-HA ↑
CASP14
DPLM-2 ( Wang et al., 2025 )
0.8820
2.8576
–
–
0.8860
0.7718
0.5724
+ Rosetta fixbb
0.8820
2.8576
0.7532
3.4918
0.8859
0.7717
0.5723
+ PDBFixer
0.8820
2.8576
0.6632
3.9657
0.8859
0.7717
0.5723
+ cg2all (nofix)
0.8820
2.8093
0.7710
3.4120
0.8859
0.7718
0.5722
+ cg2all (fixed)
0.8819
2.8576
0.7611
3.4358
0.8859
0.7717
0.5723
ADT (Ours)
0.8970
0.9628
0.8223
1.3157
0.9695
0.9398
0.7686
Table 3: Protein reconstruction performance on CASP14 and CASP15. DPLM-2 variants recover all-atom structures using different backbone-to-all-atom reconstruction methods.
Type
Method
Valid ↑
Unique ↑
Div. ↑
PB Valid ↑
Continuous
EQGAT-diff ( Le et al., 2024 )
0.99
1.00
0.89
0.94
SemlaFlow ( Irwin et al., 2024 )
0.99
0.95
0.89
0.94
FlowMol ( Dunn and Koes, 2024 )
0.97
0.97
0.92
0.94
ADiT ( Joshi et al., 2025 )
0.97
0.97
0.90
0.92
SinAE ( Ren et al., 2026 )
0.97
0.97
0.91
0.94
Discrete
Mol-StrucTok ( Gao et al., 2026 )
0.97
0.85
0.87
0.88
Table 4: Unconditional molecular generation results on QM9.
Method
Length Match
C α -lDDT
BB-lDDT
TM-score
AA-lDDT
DPLM-2
1.0
0.5607
0.5683
0.633
–
+ Rosetta fixbb
1.0
0.5607
0.5683
0.633
0.482
+ PDBFixer
1.0
0.5607
0.5683
0.633
0.372
+ cg2all nofix
1.0
0.5607
0.5683
0.633
0.503
+ cg2all fixed
1.0
0.5607
0.5683
0.633
0.496
ADT (Ours)
1.0
0.5740
0.5801
0.665
0.543
Table 5: Sequence-conditioned protein structure generation on CAMEO22.
Method
C α -lDDT ↑
BB RMSD ↓
AA lDDT ↑
AA RMSD ↓
SC RMSD ↓
TM-score ↑
GDT-TS ↑
GDT-HA ↑
CASP14
Backbone only
0.8802
1.2804
0.7699
1.9269
2.3858
0.9555
0.9038
0.7241
Separate BB+SC
0.8762
1.3105
0.8262
1.5075
1.6763
0.9549
0.9106
0.7238
Joint All-atom (ADT)
0.8970
0.9628
0.8223
1.3157
1.5938
0.9695
0.9398
0.7686
CASP15
Backbone only
0.8864
1.6517
0.7866
2.2386
2.6672
0.9365
0.8875
0.7150
Separate BB+SC
0.8827
1.4884
0.8306
1.7711
2.0341
0.9416
0.8896
0.7065
Joint All-atom (ADT)
0.8972
1.5191
0.8258
1.8261
2.0779
0.9470
0.9001
0.7285
Table 6: Ablation of protein structural encoding strategies on CASP14 and CASP15.
Figure 9
Decoder
Layers
Match ↑
RMSD ↓
PB Valid ↑
RMSD Gain ↑
Transformer
4
97.5
0.0695
0.88
27.19%
Diffusion
4
98.3
0.0506
0.89
Transformer
8
98.4
0.0636
0.90
33.18%
Diffusion
8
99.1
0.0425
0.91
Transformer
12
98.9
0.0584
0.92
41.27%
Diffusion
12
99.7
0.0343
0.93
Table 7: Effect of decoder depth on QM9 reconstruction.
Appendix figures & tables9 assets
Supplementary material from the paper’s appendix.
Appendix
Model
CASP14
CASP15
AA RMSD ↓
TM-score ↑
AA RMSD ↓
TM-score ↑
Atom-level
Bio2Token ( Liu et al., 2025 )
0.644
0.983
0.693
0.981
BiHiTo ( Zheng et al., 2026 )
0.515
0.987
0.585
0.986
Residue-level
DPLM-2 ( Wang et al., 2025 )
–
0.8860
–
0.8644
+ cg2all (no fix)
3.4120
0.8859
4.5037
0.8644
+ PDBFixer
3.9657
0.8859
5.0213
0.8644
Appendix
Table 8: All-atom protein reconstruction across token granularities on CASP14 and CASP15.
CASP14
CASP15
Method
C α -lDDT ↑
BB RMSD ↓
TM-score ↑
GDT-TS ↑
GDT-HA ↑
C α -lDDT ↑
BB RMSD ↓
TM-score ↑
GDT-TS ↑
GDT-HA ↑
ESM3
0.9653
1.9934
0.9552
0.9041
0.8068
0.9672
2.0685
0.9455
0.8693
0.7470
DPLM-2
0.8820
2.8576
0.8860
0.7718
0.5724
0.8933
4.0223
0.8644
0.7032
0.5104
ADT (Ours)
0.8970
0.9628
0.9695
0.9398
0.7686
0.8972
1.5191
0.9470
0.9001
0.7285
Appendix
Table 9: Protein structure reconstruction performance on CASP14 and CASP15.
Method
Des. ↑
Div. ↑
DPT ↓
Nov. ↑
ESM3
0.61
127
0.37
0.84
DPLM-2
0.63
130
0.37
0.72
ADT (Ours)
0.68
139
0.35
0.76
Appendix
Table 10: Unconditional protein structure generation.
Figure 5: Qualitative results of samples generated by ADT for small molecules from QM9 and proteins.
Method
C α lDDT ↑
BB RMSD ↓
AA lDDT ↑
AA RMSD ↓
SC RMSD ↓
TM-score ↑
GDT-TS ↑
GDT-HA ↑
CASP14
Shuffled
0.3100
21.166
0.2978
21.709
22.278
0.2253
0.0373
0.0058
ADT
0.8970
0.9628
0.8223
1.3157
1.5938
0.9695
0.9398
0.7686
CASP15
Shuffled
0.3233
22.245
0.3103
22.733
23.274
0.2250
0.0354
0.0057
ADT
0.8972
1.5191
0.8258
1.8261
2.0779
0.9470
0.9001
0.7285
Appendix
Table 11: Ablation of structural tokens on protein structure reconstruction.
Decoder
Match ↑
RMSD ↓
PB Valid ↑
Bond-length ↓
Bond-angle ↓
Dihedral ↓
Transformer
98.9
0.0584
0.92
0.02219
1.4971
4.5234
Diffusion
99.7
0.0343
0.93
0.01557
1.0929
3.7622
Appendix
Table 12: Fine-grained Geometric Reconstruction on QM9.
Coarse:Fine
C α lDDT ↑
BB RMSD ↓
AA lDDT ↑
AA RMSD ↓
TM-score ↑
GDT-TS ↑
GDT-HA ↑
CASP14
12:0
0.8568
1.1196
0.7934
1.5559
0.9528
0.9027
0.7089
8:4
0.8892
0.9876
0.8161
1.3574
0.9668
0.9324
0.7571
10:2
0.8970
0.9628
0.8223
1.3157
0.9695
0.9398
0.7686
0:12
0.8624
1.0738
0.8067
1.5126
0.9587
0.9068
0.7115
CASP15
12:0
0.8574
1.7668
0.7967
2.1594
0.9307
0.8630
0.6688
8:4
0.8895
1.5583
0.8196
1.8840
0.9444
0.8930
0.7170
Appendix
Table 13: Ablation of coarse-to-fine diffusion decoding on protein structure reconstruction.
Codebook
C α lDDT ↑
BB RMSD ↓
AA lDDT ↑
AA RMSD ↓
TM-score ↑
GDT-TS ↑
GDT-HA ↑
CASP14
2048
0.8634
1.0342
0.7864
1.4734
0.9563
0.9172
0.7243
4096
0.8721
0.9818
0.8013
1.3869
0.9634
0.9195
0.7431
8192
0.8970
0.9628
0.8223
1.3157
0.9695
0.9398
0.7686
16384
0.9056
0.9467
0.8315
1.2768
0.9711
0.9584
0.7869
CASP15
2048
0.8628
1.6324
0.7899
2.0413
0.9338
0.8812
0.6853
4096
0.8706
1.5587
0.8049
1.9284
0.9409
0.8876
0.7041
Appendix
Table 14: Effect of discrete codebook size on protein structure reconstruction.
Strategy
Valid ↑
Unique ↑
Div. ↑
PB Valid ↑
Interleaved AR
0.94
0.93
0.90
0.88
G2C-AR
0.92
0.89
0.91
0.85
C2G-AR
1.00
0.96
0.91
0.94
Appendix
Table 15: Effect of autoregressive factorization on QM9 generation.
Bridging molecular structures and natural language is essential for controllable design. Autoregressive models struggle with long-range dependencies, while standard diffusion processes apply uniform corruption across positions, which can distort structurally informative tokens. We present BiMol-Diff, a unified diffusion framework for the paired tasks of text-conditioned molecule generation and molecule captioning. Our key component is a token-aware noise schedule that assigns position-dependent corruption based on token recovery difficulty, preserving harder-to-recover substructures during the forward process. On ChEBI-20 and M3-20M, BiMol-Diff improves molecule reconstruction with a 15.4% relative gain in Exact Match and achieves strong captioning results, attaining best BLEU and BERTScore among compared baselines. These results indicate token-aware noising improves fidelity in molecular structure-language modelling.
Recent 3D molecular generation methods primarily use asynchronous auto-regressive or synchronous diffusion models. While auto-regressive models build molecules sequentially, they're limited by a short horizon and a discrepancy between training and inference. Conversely, synchronous diffusion models denoise all atoms at once, offering a molecule-level horizon but failing to capture the causal relationships inherent in hierarchical molecular structures. We introduce Equivariant Asynchronous Diffusion (EAD) to overcome these limitations. EAD is a novel diffusion model that combines the strengths of both approaches: it uses an asynchronous denoising schedule to better capture molecular hierarchy while maintaining a molecule-level horizon. Since these relationships are often complex, we propose a dynamic scheduling mechanism to adaptively determine the denoising timestep. Experimental results show that EAD achieves state-of-the-art performance in 3D molecular generation.
Junyi An, Chao Qu, Yun-Fei Shi +3
Shanghai Academy of Artificial Intelligence for Science, SAIS · Artificial Intelligence Innovation and Incubation (AI3) Institute, Fudan University
Protein sequence, structure, and functional annotations each capture complementary aspects of protein biology, yet existing tokenizers encode each modality independently, limiting the expressiveness of discrete protein representations. We present ProTok, a unified protein tokenizer that maps all three modalities into a modular discrete vocabulary via product quantization with per-modality codebook groups and modality dropout. A single ProTok checkpoint supports flexible inference from any modality subset without retraining. On seven StructTokenBench benchmarks spanning 14 tasks and 28 test splits, ProTok achieves an average rank of 1.4 across all structure-only tokenizers, placing first on 21 splits and among the top two on 27 of the 28. These gains come without sacrificing reconstruction: ProTok's tokens reach 0.939 lDDT on CATH 4.2, showing that multi-codebook quantization and multi-modal training yield tokens that are both reconstructable and informative. ProTok's structure tokens further lead all baseline structure tokenizers on zero-shot functional retrieval across CATH, Enzyme Commission, and Gene Ontology label hierarchies. The vocabulary also supports generation: a compact language model trained from scratch over ProTok tokens jointly generates backbone and sequence, with 52% of sampled backbones designable versus 21% for a parameter-matched GeoBPE baseline. ProTok shows that structure, sequence, and function can share one discrete vocabulary, motivating protein language models that reason over a unified token stream.
Romain Hardy, Xiaoman Zhang, Pranav Rajpurkar
Department of Biomedical Informatics, Harvard Medical School