UniCorn: A Unified Contrastive Learning Approach for Multi-view Molecular Representation Learning
Abstract
Recently, a noticeable trend has emerged in developing pre-trained foundation models in the domains of CV and NLP. However, for molecular pre-training, there lacks a universal model capable of effectively applying to various categories of molecular tasks, since existing prevalent pre-training methods exhibit effectiveness for specific types of downstream tasks. Furthermore, the lack of profound understanding of existing pre-training methods, including 2D graph masking, 2D-3D contrastive learning, and 3D denoising, hampers the advancement of molecular foundation models. In this work, we provide a unified comprehension of existing pre-training methods through the lens of contrastive learning. Thus their distinctions lie in clustering different views of molecules, which is shown beneficial to specific downstream tasks. To achieve a complete and general-purpose molecular representation, we propose a novel pre-training framework, named UniCorn, that inherits the merits of the three methods, depicting molecular views in three different levels. SOTA performance across quantum, physicochemical, and biological tasks, along with comprehensive ablation study, validate the universality and effectiveness of UniCorn.
Benchmark Results
Tested on 9 datasets 14 baseline values reported too low
Tables show presented results in global context (best 3 papers + GCN + MLP).
MoleculeNet
| # | Model | ROC-AUC ↑ | Paper |
|---|---|---|---|
| 1 | HIMP | 0.8740
±0.0050 | |
| 2 | GINE w/ VN | 0.8720
±0.0030 | |
| 3 | NaiveGINe+ K=3 w/ VN | 0.8700
±0.0040 | |
| 14 | GCN | 0.8400
±0.0040 | |
| 15 | GROVER | 0.8380
±0.0170 best reported | best at pub: KPGT: Knowledge-Guided Pre-training of Graph Transformer for Molecular Property Prediction (KDD 2022) |
| 48 | 3D Infomax | 0.8050
±0.0320 best reported | best at pub: KPGT: Knowledge-Guided Pre-training of Graph Transformer for Molecular Property Prediction (KDD 2022) |
| 61 | GraphMVP | 0.7990
±0.0180 best reported | best at pub: KPGT: Knowledge-Guided Pre-training of Graph Transformer for Molecular Property Prediction (KDD 2022) |
| 82 | UniCorn | 0.7930
±0.0050 | This paper |
| 125 | MoleBlend | 0.7780
±0.0080 | This paper |
| 150 | Mole-BERT | 0.7710
±0.0040 best reported | best at pub: UniMAP: Universal SMILES-Graph Representation Learning (2023) Difference within reported uncertainty; not counted as underperformance. |
| 161 | MoleculeSDE | 0.7680
±0.0030 | This paper |
| 202 | GraphMAE | 0.7550
±0.0060 | This paper |
| 229 | AttrMask | 0.7510
±0.0090 best reported | best at pub: Motif-aware Attribute Masking for Molecular Graph Pre-training (2023) Difference within reported uncertainty; not counted as underperformance. |
| # | Model | ROC-AUC ↑ | Paper |
|---|---|---|---|
| 1 | ProtoMol | 0.9140
±0.0030 | |
| 2 | MMSG | 0.9080
±0.0050 | |
| 3 | MemGNN | 0.9070 | |
| 43 | GIN | 0.8646
±0.0081 | |
| 59 | UniCorn | 0.8580
±0.0120 | This paper |
| 96 | MoleBlend | 0.8370
±0.0140 | This paper |
| 105 | GraphMAE | 0.8310
±0.0090 | This paper |
| 118 | GROVER | 0.8260
±0.0070 | prev best: Motif-based Graph Self-Supervised Learning for Molecular Property Prediction (NeurIPS 2021) |
| 143 | Mole-BERT | 0.8140
±0.0100 best reported | best at pub: UniMAP: Universal SMILES-Graph Representation Learning (2023) Difference within reported uncertainty; not counted as underperformance. |
| 149 | GraphMVP | 0.8120
±0.0090 best reported | best at pub: Unified 2D and 3D Pre-Training of Molecular Representations (KDD 2022) best today: Invariant-Based Diagnostics for Graph Benchmarks (2026) |
| 170 | MoleculeSDE | 0.8040
±0.0092 best reported | best at pub: A Group Symmetric Stochastic Differential Equation Model for Molecule Multi-modal Pretraining (ICML 2023) Difference within reported uncertainty; not counted as underperformance. |
| 182 | AttrMask | 0.7970
±0.0030 | This paper |
| 183 | 3D Infomax | 0.7970
±0.0150 | This paper |
| # | Model | ROC-AUC ↑ | Paper |
|---|---|---|---|
| 1 | MAGPrompt+ | 0.9432
±0.0238 | |
| 2 | CamS-LLaMA | 0.9420 | |
| 3 | SE(3)-I MPPH | 0.9400
±0.0210 | |
| 34 | GIN | 0.8875
±0.0049 | |
| 37 | GROVER | 0.8870
±0.0060 best reported | best at pub: KPGT: Knowledge-Guided Pre-training of Graph Transformer for Molecular Property Prediction (KDD 2022) |
| 41 | 3D Infomax | 0.8770
±0.0140 best reported | best at pub: KPGT: Knowledge-Guided Pre-training of Graph Transformer for Molecular Property Prediction (KDD 2022) |
| 49 | GraphMVP | 0.8600
±0.0340 best reported | best at pub: KPGT: Knowledge-Guided Pre-training of Graph Transformer for Molecular Property Prediction (KDD 2022) |
| 71 | UniCorn | 0.7420
±0.0110 | This paper |
| 80 | MoleculeSDE | 0.7320
±0.0048 best reported | best at pub: A Group Symmetric Stochastic Differential Equation Model for Molecule Multi-modal Pretraining (ICML 2023) |
| 83 | MoleBlend | 0.7300
±0.0080 | This paper |
| 96 | Mole-BERT | 0.7230
±0.0070 best reported | best at pub: UniMAP: Universal SMILES-Graph Representation Learning (2023) Difference within reported uncertainty; not counted as underperformance. |
| 101 | GraphMAE | 0.7200
±0.0060 | This paper |
| 141 | AttrMask | 0.7020
±0.0050 best reported | best at pub: 16 Pre-training Molecular Graph Representation with 3D Geometry (ICLR 2021) best today: Graph Generative Pre-trained Transformer (ICML 2025) |
| # | Model | ROC-AUC ↑ | Paper |
|---|---|---|---|
| 1 | SE(3)-I MPPH | 0.9930
±0.0040 | |
| 2 | KA-GCN | 0.9920
±0.0050 | |
| 3 | KA-GAT | 0.9910
±0.0050 | |
| 15 | UniCorn | 0.9210
±0.0040 | This paper |
| 19 | GCN | 0.9130
±0.0170 | |
| 40 | AttrMask | 0.8770
±0.0110 | This paper |
| 42 | MoleBlend | 0.8760
±0.0070 | This paper |
| 46 | MoleculeSDE | 0.8700
±0.0050 | This paper |
| 49 | GraphMVP | 0.8650
±0.0170 best reported | best at pub: A Group Symmetric Stochastic Differential Equation Model for Molecule Multi-modal Pretraining (ICML 2023) best today: SubGDiff: A Subgraph Diffusion Model to Improve Molecular Representation Learning (NeurIPS 2024) |
| 71 | GraphMAE | 0.8230
±0.0120 | This paper |
| 76 | GROVER | 0.8170
±0.0250 best reported | best at pub: UniMAP: Universal SMILES-Graph Representation Learning (2023) Difference within reported uncertainty; not counted as underperformance. |
| 88 | Mole-BERT | 0.8010
±0.0360 best reported | best at pub: UniMAP: Universal SMILES-Graph Representation Learning (2023) Difference within reported uncertainty; not counted as underperformance. |
| 89 | 3D Infomax | 0.7990
±0.0340 | This paper |
| # | Model | ROC-AUC ↑ | Paper |
|---|---|---|---|
| 1 | KA-GAT | 0.8470
±0.0020 | |
| 2 | KA-GCN | 0.8420
±0.0010 | |
| 3 | GraphKAN | 0.8370
±0.0010 | |
| 50 | MoleBlend | 0.6490
±0.0030 | This paper |
| 52 | GROVER | 0.6480
±0.0060 | |
| 66 | GIN | 0.6403
±0.0104 | |
| 69 | UniCorn | 0.6400
±0.0180 | This paper |
| 70 | GraphMVP | 0.6390
±0.0120 best reported | best at pub: Unified 2D and 3D Pre-Training of Molecular Representations (KDD 2022) best today: A Systematic Survey and Benchmark of Deep Learning for Molecular Property Prediction in the Foundation Model Era (2026) Difference within reported uncertainty; not counted as underperformance. |
| 90 | Mole-BERT | 0.6280
±0.0110 | This paper |
| 134 | AttrMask | 0.6120
±0.0010 | This paper |
| 148 | MoleculeSDE | 0.6080
±0.0030 | This paper |
| 155 | 3D Infomax | 0.6060
±0.0070 | This paper |
| 175 | GraphMAE | 0.6030
±0.0110 | This paper |
| # | Model | ROC-AUC ↑ | Paper |
|---|---|---|---|
| 1 | GeomGCL | 0.7630 | |
| 2 | LiGhT DeepGPT | 0.7570
±0.0110 | |
| 3 | CoMPT | 0.7550 | |
| 14 | GCN | 0.7350
±0.0020 | |
| 25 | 3D Infomax | 0.7160
±0.0130 best reported | best at pub: KPGT: Knowledge-Guided Pre-training of Graph Transformer for Molecular Property Prediction (KDD 2022) |
| 34 | GROVER | 0.7080
±0.0150 best reported | best at pub: KPGT: Knowledge-Guided Pre-training of Graph Transformer for Molecular Property Prediction (KDD 2022) |
| 43 | UniCorn | 0.6940
±0.0110 | This paper |
| 50 | GraphMVP | 0.6890
±0.0100 best reported | best at pub: KPGT: Knowledge-Guided Pre-training of Graph Transformer for Molecular Property Prediction (KDD 2022) |
| 87 | MoleBlend | 0.6610 | This paper |
| 103 | MoleculeSDE | 0.6520
±0.0031 best reported | best at pub: A Group Symmetric Stochastic Differential Equation Model for Molecule Multi-modal Pretraining (ICML 2023) Difference within reported uncertainty; not counted as underperformance. |
| 114 | Mole-BERT | 0.6450
±0.0040 best reported | best at pub: UniMAP: Universal SMILES-Graph Representation Learning (2023) Difference within reported uncertainty; not counted as underperformance. |
| 128 | GraphMAE | 0.6410
±0.0030 | This paper |
| 150 | AttrMask | 0.6330
±0.0060 best reported | best at pub: Motif-aware Attribute Masking for Molecular Graph Pre-training (2023) Difference within reported uncertainty; not counted as underperformance. |
| # | Model | RMSE ↓ | Paper |
|---|---|---|---|
| 1 | Graphormer-SPIS | 0.4840
±0.0050 | |
| 2 | Graphormer-SPD | 0.4920
±0.0040 | |
| 3 | conan-FGW | 0.5140
±0.0190 | |
| 7 | GCN | 0.5640
±0.0150 | |
| 49 | UniCorn | 0.8170
±0.0340 | This paper |
| # | Model | RMSE ↓ | Paper |
|---|---|---|---|
| 1 | SE(3)-I MPPH | 0.3540
±0.0530 | |
| 2 | ECFP-4 + RF | 0.5600
±0.0660 | |
| 3 | GPSE + GPS | 0.6820 | |
| 28 | UniCorn(DFT + RDKit) | 1.5550
±0.0750 | This paper |
| 69 | GIN | 2.3460
±0.1220 |
Quantum Chemistry
| # | Model | MAE ↓ | Paper |
|---|---|---|---|
| 1 | QHNet | 0.0000 | |
| 2 | QHNetV2 | 0.0000 | |
| 3 | PhiSNet | 0.0000 | |
| 42 | Frad | 0.0431 best reported | best today: 3D-GSRD: 3D Molecular Graph Auto-Encoder with Selective Re-mask Decoding (2025) |
| 43 | UniCorn | 0.0460 | This paper |
| 58 | Coord | 0.0529 best reported | best at pub: Sliced Denoising: A Physics-Informed Molecular Pre-Training Method (ICLR 2023) |
| 86 | SE(3)-DDM | 0.1220 | This paper |
| 104 | MoleculeSDE | 0.2820 | |
| 106 | MoleculeJAE | 0.3450 | This paper |
