A Systematic Survey and Benchmark of Deep Learning for Molecular Property Prediction in the Foundation Model Era
Abstract
Molecular property prediction integrates quantum chemistry, cheminformatics, and deep learning to connect molecular structure with physicochemical and biological behavior. This survey traces four complementary paradigms, including Quantum, Descriptor Machine Learning, Geometric Deep Learning, and Foundation Models, and outlines a unified taxonomy linking molecular representations, model architectures, and interdisciplinary applications. Benchmark analyses integrate evidence from both widely used data sets and data sets reflecting industry perspectives, encompassing quantum, physicochemical, physiological, and biophysical domains. The survey examines current standards in data curation, splitting strategies, and evaluation protocols, highlighting challenges including inconsistent stereochemistry, heterogeneous assay sources, and reproducibility limitations under random or poorly defined splits. These observations motivate the modernization of benchmark design toward more transparent, time- and scaffold-aware methodologies. We further propose three forward-looking directions: (i) physics-aware learning embedding quantum consistency, (ii) uncertainty-calibrated foundation models for trustworthy inference, and (iii) realistic multimodal benchmark ecosystems integrating computational and experimental data. Repository: https://github.com/Zongru-Li/Survey-and-Benchmarks-of-DL-for-Molecular-Property-Prediction-in-the-Foundation-Model-Era.
Benchmark Results
Tested on 5 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 | |
| 18 | AttentiveFP | 0.8350 best reported | best at pub: GeomGCL: Geometric Graph Contrastive Learning for Molecular Property Prediction (AAAI 2021) |
| 57 | KA-GAT | 0.8000
±0.0060 | This paper |
| 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) |
| 65 | KA-GCN | 0.7990
±0.0050 | This paper |
| 67 | MolCLR | 0.7980
±0.0070 best reported | |
| 69 | SMPT | 0.7970
±0.0010 | This paper |
| 72 | Uni-Mol | 0.7960
±0.0050 | prev best: Motif-aware Attribute Masking for Molecular Graph Pre-training (2023) Improvement within reported uncertainty; not highlighted. |
| 79 | Mol-GDL | 0.7940
±0.0050 | This paper |
| 93 | D-MPNN | 0.7890
±0.0130 best reported | |
| 119 | PretrainGNN | 0.7810
±0.0060 | This paper |
| 120 | GEM | 0.7810
±0.0010 | This paper |
| 192 | N-GramXGB | 0.7580
±0.0090 | This paper |
| 215 | GraphKAN | 0.7530
±0.0070 | This paper |
| 242 | GNN-SKAN | 0.7470
±0.0050 | This paper |
| 258 | N-GramRF | 0.7430
±0.0090 | This paper |
| 283 | KA-GNNs | 0.7300
±0.0120 | This paper |
| # | Model | ROC-AUC ↑ | Paper |
|---|---|---|---|
| 1 | ProtoMol | 0.9140
±0.0030 | |
| 2 | MMSG | 0.9080
±0.0050 | |
| 3 | MemGNN | 0.9070 | |
| 9 | MolCLR | 0.8900
±0.0030 best reported | |
| 10 | KA-GCN | 0.8900
±0.0140 | This paper |
| 14 | KA-GAT | 0.8840
±0.0040 | This paper |
| 20 | D-MPNN | 0.8780
±0.0320 best reported | best at pub: SE(3)-Invariant Multiparameter Persistent Homology for Chiral-Sensitive Molecular Property Prediction (NeurIPS 2023) |
| 25 | SMPT | 0.8730
±0.0150 | This paper |
| 43 | GIN | 0.8646
±0.0081 | |
| 45 | AttentiveFP | 0.8630
±0.0150 best reported | best at pub: Molformer: Motif-based Transformer on 3D Heterogeneous Molecular Graphs (AAAI 2021) |
| 46 | Mol-GDL | 0.8630
±0.0190 | This paper |
| 61 | Uni-Mol | 0.8570
±0.0020 | This paper |
| 62 | GEM | 0.8560
±0.0110 | This paper |
| 83 | PretrainGNN | 0.8450
±0.0070 | This paper |
| 126 | GraphKAN | 0.8230
±0.0110 | This paper |
| 149 | GraphMVP | 0.8120
±0.0090 | This paper |
| 201 | N-GramXGB | 0.7910
±0.0130 | This paper |
| 218 | N-GramRF | 0.7790
±0.0150 | This paper |
| 250 | KA-GNNs | 0.7520
±0.0110 | This paper |
| 253 | GNN-SKAN | 0.7470
±0.0090 | 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 | |
| 26 | D-MPNN | 0.9130
±0.0260 best reported | best at pub: SE(3)-Invariant Multiparameter Persistent Homology for Chiral-Sensitive Molecular Property Prediction (NeurIPS 2023) |
| 31 | AttentiveFP | 0.9080
±0.0500 best reported | best at pub: Molformer: Motif-based Transformer on 3D Heterogeneous Molecular Graphs (AAAI 2021) |
| 34 | GIN | 0.8875
±0.0049 | |
| 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) |
| 62 | KA-GCN | 0.7870
±0.0140 | This paper |
| 63 | KA-GAT | 0.7850
±0.0210 | This paper |
| 78 | MolCLR | 0.7360
±0.0050 best reported | best at pub: How Much Structural Information Large Scale Molecular Language Representations Can Capture? (2021) best today: Improving Molecular Contrastive Learning via Faulty Negative Mitigation and Decomposed Fragment Contrast (2022) Difference within reported uncertainty; not counted as underperformance. |
| 79 | SMPT | 0.7340
±0.0030 | This paper |
| 81 | GraphKAN | 0.7310
±0.0170 | This paper |
| 84 | Uni-Mol | 0.7290
±0.0060 | prev best: Motif-aware Attribute Masking for Molecular Graph Pre-training (2023) |
| 88 | Mol-GDL | 0.7280
±0.0190 | This paper |
| 93 | GEM | 0.7240
±0.0040 | This paper |
| 98 | KA-GNNs | 0.7210
±0.0030 | This paper |
| 160 | N-GramRF | 0.6970
±0.0060 | This paper |
| 177 | N-GramXGB | 0.6910
±0.0080 | This paper |
| 186 | PretrainGNN | 0.6870
±0.0130 | This paper |
| 216 | GNN-SKAN | 0.6760
±0.0140 | This paper |
| # | Model | ROC-AUC ↑ | Paper |
|---|---|---|---|
| 1 | SE(3)-I MPPH | 0.9930
±0.0040 | |
| 2 | KA-GCN | 0.9920
±0.0050 | This paper |
| 3 | KA-GAT | 0.9910
±0.0050 | This paper |
| 4 | GraphKAN | 0.9840
±0.0030 | This paper |
| 6 | KA-GNNs | 0.9720
±0.0010 | This paper |
| 7 | Mol-GDL | 0.9660
±0.0020 | This paper |
| 11 | AttentiveFP | 0.9330
±0.0200 best reported | best at pub: Molformer: Motif-based Transformer on 3D Heterogeneous Molecular Graphs (AAAI 2021) |
| 12 | MolCLR | 0.9320
±0.0170 best reported | best at pub: Improving Molecular Contrastive Learning via Faulty Negative Mitigation and Decomposed Fragment Contrast (2022) Difference within reported uncertainty; not counted as underperformance. |
| 13 | SMPT | 0.9270
±0.0020 | This paper |
| 17 | Uni-Mol | 0.9190
±0.0180 | prev best: Motif-aware Attribute Masking for Molecular Graph Pre-training (2023) |
| 19 | GCN | 0.9130
±0.0170 | |
| 23 | D-MPNN | 0.9060
±0.0070 | This paper |
| 24 | GEM | 0.9010
±0.0130 | prev best: MolGA: Molecular Graph Adaptation with Pre-trained 2D Graph Encoder (2025) |
| 45 | N-GramXGB | 0.8750
±0.0270 | 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) |
| 112 | N-GramRF | 0.7750
±0.0400 | This paper |
| 155 | PretrainGNN | 0.7260
±0.0150 | This paper |
| # | Model | ROC-AUC ↑ | Paper |
|---|---|---|---|
| 1 | KA-GAT | 0.8470
±0.0020 | This paper |
| 2 | KA-GCN | 0.8420
±0.0010 | This paper |
| 3 | GraphKAN | 0.8370
±0.0010 | This paper |
| 4 | Mol-GDL | 0.8310
±0.0020 | This paper |
| 5 | KA-GNNs | 0.8310
±0.0040 | This paper |
| 14 | MolCLR | 0.6800
±0.0110 best reported | |
| 15 | SMPT | 0.6760
±0.0500 | This paper |
| 18 | GEM | 0.6720
±0.0040 | prev best: MolGA: Molecular Graph Adaptation with Pre-trained 2D Graph Encoder (2025) |
| 26 | N-GramRF | 0.6680
±0.0070 | This paper |
| 37 | Uni-Mol | 0.6590
±0.0130 | prev best: Motif-aware Attribute Masking for Molecular Graph Pre-training (2023) |
| 43 | N-GramXGB | 0.6550
±0.0070 | This paper |
| 66 | GIN | 0.6403
±0.0104 | |
| 70 | GraphMVP | 0.6390
±0.0120 | This paper |
| 82 | D-MPNN | 0.6320
±0.0230 best reported | |
| 91 | PretrainGNN | 0.6270
±0.0080 | This paper |
| 130 | GNN-SKAN | 0.6140
±0.0050 | This paper |
| 157 | AttentiveFP | 0.6060
±0.0320 | This paper |
