MolGA: Molecular Graph Adaptation with Pre-trained 2D Graph Encoder
Abstract
Molecular graph representation learning is widely used in chemical and biomedical research. While pre-trained 2D graph encoders have demonstrated strong performance, they overlook the rich molecular domain knowledge associated with submolecular instances (atoms and bonds). While molecular pre-training approaches incorporate such knowledge into their pre-training objectives, they typically employ designs tailored to a specific type of knowledge, lacking the flexibility to integrate diverse knowledge present in molecules. Hence, reusing widely available and well-validated pre-trained 2D encoders, while incorporating molecular domain knowledge during downstream adaptation, offers a more practical alternative. In this work, we propose MolGA, which adapts pre-trained 2D graph encoders to downstream molecular applications by flexibly incorporating diverse molecular domain knowledge. First, we propose a molecular alignment strategy that bridge the gap between pre-trained topological representations with domain-knowledge representations. Second, we introduce a conditional adaptation mechanism that generates instance-specific tokens to enable fine-grained integration of molecular domain knowledge for downstream tasks. Finally, we conduct extensive experiments on eleven public datasets, demonstrating the effectiveness of MolGA.
Benchmark Results
Tested on 7 datasets 36 baseline values reported too low
Tables show presented results in global context (best 3 papers + GCN + MLP).
MoleculeNet
| # | 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 | |
| 52 | GAT | 0.8600
±0.0110 best reported | best at pub: Optimal Transport Graph Neural Networks (2020) |
| 62 | GEM | 0.8560
±0.0110 best reported | best at pub: How Much Structural Information Large Scale Molecular Language Representations Can Capture? (2021) best today: Invariant-Based Diagnostics for Graph Benchmarks (2026) |
| 64 | GCN | 0.8540
±0.0110 best reported | best at pub: Atom-Motif Contrastive Transformer for Molecular Property Prediction (2023) |
| 96 | MoleBlend | 0.8370
±0.0146 best reported | |
| 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) |
| 213 | GraphCL | 0.7820
±0.0120 best reported | best at pub: Omni-Granular Ego-Semantic Propagation for Self-Supervised Graph Representation Learning (ICML 2022) |
| 290 | GraphPrompt | 0.6770
±0.0126 best reported | best at pub: Universal Prompt Tuning for Graph Neural Networks (NeurIPS 2022) |
| 310 | MolGA | 0.5494
±0.0537 | This paper |
| 311 | ComENet | 0.5457
±0.1021 | This paper |
| 312 | SphereNet | 0.5443
±0.1341 | This paper |
| 313 | DimeNet++ | 0.5406
±0.1300 | 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 | |
| 36 | GraphCL | 0.8870
±0.0190 best reported | best at pub: KPGT: Knowledge-Guided Pre-training of Graph Transformer for Molecular Property Prediction (KDD 2022) |
| 38 | GCN | 0.8810
±0.0360 best reported | best at pub: Motif-based Graph Representation Learning with Application to Chemical Molecules (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) |
| 83 | MoleBlend | 0.7300
±0.0081 best reported | best at pub: UniCorn: A Unified Contrastive Learning Approach for Multi-view Molecular Representation Learning (ICML 2024) best today: A Generalist Cross-Domain Molecular Learning Framework for Structure-Based Drug Discovery (2025) Difference within reported uncertainty; not counted as underperformance. |
| 93 | GEM | 0.7240
±0.0040 best reported | best at pub: How Much Structural Information Large Scale Molecular Language Representations Can Capture? (2021) best today: Invariant-Based Diagnostics for Graph Benchmarks (2026) Difference within reported uncertainty; not counted as underperformance. |
| 106 | MolGA | 0.7197
±0.1234 | This paper |
| 171 | GraphPrompt | 0.6929
±0.0019 best reported | best at pub: Universal Prompt Tuning for Graph Neural Networks (NeurIPS 2022) Difference within reported uncertainty; not counted as underperformance. |
| 210 | GAT | 0.6776 best reported | best at pub: Application of Graph Neural Networks and graph descriptors for graph classification (2022) Difference within reported uncertainty; not counted as underperformance. |
| 239 | ComENet | 0.6689
±0.0994 | This paper |
| 245 | DimeNet++ | 0.6641
±0.1043 | This paper |
| 264 | SphereNet | 0.6554
±0.1051 | This paper |
| # | 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 | |
| 19 | GCN | 0.9130
±0.0170 best reported | best at pub: OOD-GNN: Out-of-Distribution Generalized Graph Neural Network (2021) |
| 24 | GEM | 0.9010
±0.0130 best reported | |
| 36 | GIN | 0.8810
±0.0250 | |
| 42 | MoleBlend | 0.8760
±0.0075 best reported | |
| 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) |
| 66 | GAT | 0.8260
±0.0450 best reported | best at pub: Robust Ante-hoc Graph Explainer using Bilevel Optimization (2023) |
| 97 | GraphCL | 0.7890
±0.0420 best reported | best at pub: 16 Pre-training Molecular Graph Representation with 3D Geometry (ICLR 2021) best today: Improving Molecular Pretraining with Complementary Featurizations (2022) |
| 121 | DimeNet++ | 0.7600 best reported | best at pub: GeomGCL: Geometric Graph Contrastive Learning for Molecular Property Prediction (AAAI 2021) |
| 234 | MolGA | 0.5731
±0.0687 | This paper |
| 237 | ComENet | 0.5589
±0.0909 | This paper |
| 239 | GraphPrompt | 0.5567
±0.0708 | prev best: Universal Prompt Tuning for Graph Neural Networks (NeurIPS 2022) Improvement within reported uncertainty; not highlighted. |
| 241 | SphereNet | 0.5383
±0.1087 | 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 | |
| 18 | GEM | 0.6720
±0.0040 best reported | |
| 50 | MoleBlend | 0.6490
±0.0035 best reported | |
| 66 | GIN | 0.6403
±0.0104 | |
| 70 | GraphMVP | 0.6390
±0.0120 best reported | best at pub: Unified 2D and 3D Pre-Training of Molecular Representations (KDD 2022) |
| 114 | GraphCL | 0.6183
±0.0060 best reported | |
| 125 | GCN | 0.6150
±0.0250 best reported | best at pub: Motif-based Graph Representation Learning with Application to Chemical Molecules (2022) |
| 126 | DimeNet++ | 0.6150 best reported | best at pub: GeomGCL: Geometric Graph Contrastive Learning for Molecular Property Prediction (AAAI 2021) |
| 206 | GraphPrompt | 0.5871
±0.0013 best reported | best at pub: Universal Prompt Tuning for Graph Neural Networks (NeurIPS 2022) |
| 236 | MolGA | 0.5261
±0.0542 | This paper |
| 238 | GAT | 0.5084
±0.0550 | This paper |
| 239 | ComENet | 0.5052
±0.0622 | This paper |
| 240 | SphereNet | 0.5026
±0.0592 | This paper |
| # | Model | RMSE ↓ | Paper |
|---|---|---|---|
| 1 | Graphormer-SPIS | 0.4840
±0.0050 | |
| 2 | Graphormer-SPD | 0.4920
±0.0040 | |
| 3 | conan-FGW | 0.5140
±0.0190 | |
| 5 | GAT | 0.5520
±0.0070 best reported | best at pub: On Structural Expressive Power of Graph Transformers (KDD 2023) |
| 7 | GCN | 0.5640
±0.0150 best reported | best at pub: On Structural Expressive Power of Graph Transformers (KDD 2023) |
| 18 | GraphSAGE | 0.6010
±0.0080 | |
| 26 | DimeNet++ | 0.6330 best reported | best at pub: GeomGCL: Geometric Graph Contrastive Learning for Molecular Property Prediction (AAAI 2021) |
| 79 | GraphCL | 0.9590
±0.0470 best reported | best at pub: 3D Infomax improves GNNs for Molecular Property Prediction (ICML 2021) best today: SE(3)-Invariant Multiparameter Persistent Homology for Chiral-Sensitive Molecular Property Prediction (NeurIPS 2023) |
| 98 | GraphMVP | 1.0910
±0.0210 best reported | best at pub: 16 Pre-training Molecular Graph Representation with 3D Geometry (ICLR 2021) best today: Improving Molecular Pretraining with Complementary Featurizations (2022) |
| 111 | GEM | 1.1750
±0.0200 | This paper |
| 128 | MoleBlend | 1.4960
±0.0320 | This paper |
| 141 | MolGA | 1.9730
±0.0430 | This paper |
| 143 | GraphPrompt | 2.0520
±0.0450 | This paper |
| 144 | SphereNet | 2.1350
±0.1510 | This paper |
| 147 | ComENet | 2.3170
±0.2100 | 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 | |
| 10 | DimeNet++ | 0.9780 best reported | best at pub: GeomGCL: Geometric Graph Contrastive Learning for Molecular Property Prediction (AAAI 2021) |
| 39 | MoleBlend | 1.8510
±0.0680 | This paper |
| 47 | GEM | 1.9570
±0.0730 | This paper |
| 69 | GIN | 2.3460
±0.1220 | |
| 77 | GCN | 2.6180
±0.2980 best reported | best at pub: Graph Neural Networks with a Distribution of Parametrized Graphs (ICML 2023) |
| 86 | GraphMVP | 2.7670
±0.0330 | This paper |
| 95 | GAT | 2.9420
±0.5910 best reported | best at pub: Graph Neural Networks with a Distribution of Parametrized Graphs (ICML 2023) |
| 101 | GraphCL | 3.1660
±0.0270 best reported | |
| 110 | MolGA | 3.6020
±0.1310 | This paper |
| 113 | SphereNet | 3.9000
±0.1380 | This paper |
| 116 | ComENet | 4.0490
±0.2850 | This paper |
| 120 | GraphPrompt | 4.5170
±0.1290 | This paper |
| # | Model | RMSE ↓ | Paper |
|---|---|---|---|
| 1 | MemGNN | 0.5560
±0.0230 | |
| 2 | ProtoS-L2 | 0.5800
±0.0160 | |
| 3 | ProtoW-L2 | 0.6040
±0.0140 | |
| 7 | GCN | 0.6550
±0.0360 best reported | best at pub: Memory-Based Graph Networks (ICLR 2020) |
| 9 | GIN | 0.6580
±0.0190 | |
| 24 | GraphCL | 0.7140
±0.0110 best reported | best at pub: SE(3)-Invariant Multiparameter Persistent Homology for Chiral-Sensitive Molecular Property Prediction (NeurIPS 2023) |
| 27 | GraphMVP | 0.7180 best reported | best at pub: Improving Molecular Pretraining with Complementary Featurizations (2022) best today: 3D Molecular Geometry Analysis with 2D Graphs (2023) |
| 40 | DimeNet++ | 0.7420 best reported | best at pub: GeomGCL: Geometric Graph Contrastive Learning for Molecular Property Prediction (AAAI 2021) |
| 43 | GAT | 0.7530 best reported | |
| 49 | MoleBlend | 0.7740
±0.0120 | This paper |
| 67 | GEM | 0.8400
±0.2200 | This paper |
| 97 | MolGA | 1.1870
±0.0150 | This paper |
| 98 | GraphPrompt | 1.2420
±0.0170 | This paper |
| 100 | ComENet | 1.3090
±0.0480 | This paper |
| 101 | SphereNet | 1.3350
±0.1270 | This paper |
