A Systematic Survey and Benchmark of Deep Learning for Molecular Property Prediction in the Foundation Model Era

Zongru Li, Xingsheng Chen, Honggang Wen, Regina Qianru Zhang, Ming Li, Xiaojin Zhang, Hongzhi Yin, Qiang Yang, Kwok-Yan Lam, Pietro Lio, Siu-Ming Yiu

Main figure for 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

#ModelROC-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
actual #18 vs paper #118 100 places worse
0.8350
best reported
actual #18 vs paper #118 100 places worse
paper 0.7810 ±0.0050
paper 0.7810 ±0.0050 Δ at pub 0.0540
57
KA-GAT
0.8000 ±0.0060
This paper
61
GraphMVP
actual #61 vs paper #183 122 places worse
0.7990 ±0.0180
best reported
actual #61 vs paper #183 122 places worse
paper 0.7590 ±0.0050
paper 0.7590 ±0.0050 Δ at pub 0.0400
65
KA-GCN
0.7990 ±0.0050
This paper
67
MolCLR
actual #67 vs paper #231 164 places worse
0.7980 ±0.0070
best reported
actual #67 vs paper #231 164 places worse
paper 0.7500 ±0.0020
69
SMPT
0.7970 ±0.0010
This paper
72
Uni-Mol
actual #72 vs paper #72
0.7960 ±0.0050
actual #72 vs paper #72
paper 0.7960 ±0.0050

Improvement within reported uncertainty; not highlighted.

paper 0.7960 ±0.0050 Δ at pub 0.0070
79
Mol-GDL
0.7940 ±0.0050
This paper
93
D-MPNN
actual #93 vs paper #183 90 places worse
0.7890 ±0.0130
best reported
actual #93 vs paper #183 90 places worse
paper 0.7590 ±0.0070
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
#ModelROC-AUC ↑Paper
1
ProtoMol
0.9140 ±0.0030
2
MMSG
0.9080 ±0.0050
3
MemGNN
0.9070
9
MolCLR
actual #9 vs paper #120 111 places worse
0.8900 ±0.0030
best reported
actual #9 vs paper #120 111 places worse
paper 0.8240 ±0.0090
10
KA-GCN
0.8900 ±0.0140
This paper
14
KA-GAT
0.8840 ±0.0040
This paper
20
D-MPNN
actual #20 vs paper #162 142 places worse
0.8780 ±0.0320
best reported
actual #20 vs paper #162 142 places worse
paper 0.8090 ±0.0060
25
SMPT
0.8730 ±0.0150
This paper
43
GIN
0.8646 ±0.0081
45
AttentiveFP
actual #45 vs paper #211 166 places worse
0.8630 ±0.0150
best reported
actual #45 vs paper #211 166 places worse
paper 0.7840 ±0.0220
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
#ModelROC-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
actual #26 vs paper #121 95 places worse
0.9130 ±0.0260
best reported
actual #26 vs paper #121 95 places worse
paper 0.7100 ±0.0030
31
AttentiveFP
actual #31 vs paper #248 217 places worse
0.9080 ±0.0500
best reported
actual #31 vs paper #248 217 places worse
paper 0.6630 ±0.0180
34
GIN
0.8875 ±0.0049
49
GraphMVP
actual #49 vs paper #92 43 places worse
0.8600 ±0.0340
best reported
actual #49 vs paper #92 43 places worse
paper 0.7240 ±0.0160
paper 0.7240 ±0.0160 Δ at pub 0.1360
62
KA-GCN
0.7870 ±0.0140
This paper
63
KA-GAT
0.7850 ±0.0210
This paper
78
MolCLR
actual #78 vs paper #96 18 places worse
0.7360 ±0.0050
best reported
actual #78 vs paper #96 18 places worse
paper 0.7220 ±0.0210

Difference within reported uncertainty; not counted as underperformance.

paper 0.7220 ±0.0210 Δ at pub 0.0140 Δ today 0.0140
79
SMPT
0.7340 ±0.0030
This paper
81
GraphKAN
0.7310 ±0.0170
This paper
84
Uni-Mol
actual #84 vs paper #84
0.7290 ±0.0060
actual #84 vs paper #84
paper 0.7290 ±0.0060
paper 0.7290 ±0.0060 Δ at pub 0.0750
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
#ModelROC-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
actual #11 vs paper #58 47 places worse
0.9330 ±0.0200
best reported
actual #11 vs paper #58 47 places worse
paper 0.8470 ±0.0030
12
MolCLR
actual #12 vs paper #19 7 places worse
0.9320 ±0.0170
best reported
actual #12 vs paper #19 7 places worse
paper 0.9120 ±0.0350

Difference within reported uncertainty; not counted as underperformance.

paper 0.9120 ±0.0350 Δ at pub 0.0200
13
SMPT
0.9270 ±0.0020
This paper
17
Uni-Mol
actual #17 vs paper #17
0.9190 ±0.0180
actual #17 vs paper #17
paper 0.9190 ±0.0180
paper 0.9190 ±0.0180 Δ at pub 0.1070
19
GCN
0.9130 ±0.0170
23
D-MPNN
0.9060 ±0.0070
This paper
24
GEM
actual #24 vs paper #24
0.9010 ±0.0130
actual #24 vs paper #24
paper 0.9010 ±0.0130
paper 0.9010 ±0.0130 Δ at pub 0.2778
45
N-GramXGB
0.8750 ±0.0270
This paper
49
GraphMVP
actual #49 vs paper #95 46 places worse
0.8650 ±0.0170
best reported
actual #49 vs paper #95 46 places worse
paper 0.7910 ±0.0280
112
N-GramRF
0.7750 ±0.0400
This paper
155
PretrainGNN
0.7260 ±0.0150
This paper
#ModelROC-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
actual #14 vs paper #204 190 places worse
0.6800 ±0.0110
best reported
actual #14 vs paper #204 190 places worse
paper 0.5890 ±0.0140
15
SMPT
0.6760 ±0.0500
This paper
18
GEM
actual #18 vs paper #18
0.6720 ±0.0040
actual #18 vs paper #18
paper 0.6720 ±0.0040
paper 0.6720 ±0.0040 Δ at pub 0.1303
26
N-GramRF
0.6680 ±0.0070
This paper
37
Uni-Mol
actual #37 vs paper #37
0.6590 ±0.0130
actual #37 vs paper #37
paper 0.6590 ±0.0130
paper 0.6590 ±0.0130 Δ at pub 0.0820
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
actual #82 vs paper #223 141 places worse
0.6320 ±0.0230
best reported
actual #82 vs paper #223 141 places worse
paper 0.5700 ±0.0070
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
SOTA performance (not significantly different from the best) Baseline / comparison (this paper) Global context (other papers) Best at pub — reported result worse than the best known when published (best reported in green) Best at pub — reported value improved over the best known when published