Atom-Motif Contrastive Transformer for Molecular Property Prediction

Wentao Yu, Shuo Chen, Chen Gong, Gang Niu, Masashi Sugiyama

Main figure for Atom-Motif Contrastive Transformer for Molecular Property Prediction

Abstract

Recently, Graph Transformer (GT) models have been widely used in the task of Molecular Property Prediction (MPP) due to their high reliability in characterizing the latent relationship among graph nodes (i.e., the atoms in a molecule). However, most existing GT-based methods usually explore the basic interactions between pairwise atoms, and thus they fail to consider the important interactions among critical motifs (e.g., functional groups consisted of several atoms) of molecules. As motifs in a molecule are significant patterns that are of great importance for determining molecular properties (e.g., toxicity and solubility), overlooking motif interactions inevitably hinders the effectiveness of MPP. To address this issue, we propose a novel Atom-Motif Contrastive Transformer (AMCT), which not only explores the atom-level interactions but also considers the motif-level interactions. Since the representations of atoms and motifs for a given molecule are actually two different views of the same instance, they are naturally aligned to generate the self-supervisory signals for model training. Meanwhile, the same motif can exist in different molecules, and hence we also employ the contrastive loss to maximize the representation agreement of identical motifs across different molecules. Finally, in order to clearly identify the motifs that are critical in deciding the properties of each molecule, we further construct a property-aware attention mechanism into our learning framework. Our proposed AMCT is extensively evaluated on seven popular benchmark datasets, and both quantitative and qualitative results firmly demonstrate its effectiveness when compared with the state-of-the-art methods.

Proposed method: AMCT

Benchmark Results

Tested on 6 datasets 10 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
actual #14 vs paper #144 130 places worse
0.8400 ±0.0040
best reported
actual #14 vs paper #144 130 places worse
paper 0.7720 ±0.0410
paper 0.7720 ±0.0410 Δ at pub 0.0680
20
MAT
actual #20 vs paper #104 84 places worse
0.8340
best reported
actual #20 vs paper #104 84 places worse
paper 0.7850 ±0.0110
paper 0.7850 ±0.0110 Δ at pub 0.0490
24
GIN
0.8290 ±0.0069
33
Weave
actual #33 vs paper #260 227 places worse
0.8200 ±0.0100
best reported
actual #33 vs paper #260 227 places worse
paper 0.7410 ±0.0440
best at pub: Memory-Based Graph Networks (ICLR 2020)
paper 0.7410 ±0.0440 Δ at pub 0.0790
49
AMCT
0.8040 ±0.0100
This paper
88
R-MAT
0.7910 ±0.0090
This paper
91
Graphormer
0.7900 ±0.0110
This paper
106
GREA-GCN
0.7850 ±0.0080
This paper
109
Molformer
0.7830 ±0.0120
This paper
146
SchNet
actual #146 vs paper #162 16 places worse
0.7720 ±0.0230
best reported
actual #146 vs paper #162 16 places worse
paper 0.7670 ±0.0250

Difference within reported uncertainty; not counted as underperformance.

paper 0.7670 ±0.0250 Δ at pub 0.0050
172
MGSSL
actual #172 vs paper #174 2 places worse
0.7650 ±0.0030
best reported
actual #172 vs paper #174 2 places worse
paper 0.7640 ±0.0040

Difference within reported uncertainty; not counted as underperformance.

paper 0.7640 ±0.0040 Δ at pub 0.0010
298
MGCN
0.7070 ±0.0160
This paper
304
TF-Robust
0.6980 ±0.0120
This paper
#ModelROC-AUC ↑Paper
1
ProtoMol
0.9140 ±0.0030
2
MMSG
0.9080 ±0.0050
3
MemGNN
0.9070
7
AMCT
0.8950 ±0.0120
This paper
13
Molformer
actual #13 vs paper #16 3 places worse
0.8840
best reported
actual #13 vs paper #16 3 places worse
paper 0.8810 ±0.0140

Difference within reported uncertainty; not counted as underperformance.

paper 0.8810 ±0.0140 Δ at pub 0.0030
28
R-MAT
actual #28 vs paper #57 29 places worse
0.8710
best reported
actual #28 vs paper #57 29 places worse
paper 0.8580 ±0.0410

Difference within reported uncertainty; not counted as underperformance.

paper 0.8580 ±0.0410 Δ at pub 0.0130
43
GIN
0.8646 ±0.0081
53
Graphormer
actual #53 vs paper #53
0.8600 ±0.0130
actual #53 vs paper #53
paper 0.8600 ±0.0130
paper 0.8600 ±0.0130 Δ at pub 0.0840
64
GCN
actual #64 vs paper #64
0.8540 ±0.0110
actual #64 vs paper #64
paper 0.8540 ±0.0110

Improvement within reported uncertainty; not highlighted.

paper 0.8540 ±0.0110 Δ at pub 0.0430
81
MAT
0.8460 ±0.0250
This paper
121
TF-Robust
0.8240 ±0.0220
This paper
130
MGSSL
actual #130 vs paper #181 51 places worse
0.8203 ±0.0379
best reported
actual #130 vs paper #181 51 places worse
paper 0.7970 ±0.0080

Difference within reported uncertainty; not counted as underperformance.

paper 0.7970 ±0.0080 Δ today 0.0233
167
Weave
actual #167 vs paper #199 32 places worse
0.8060 ±0.0020
best reported
actual #167 vs paper #199 32 places worse
paper 0.7910 ±0.0080
best at pub: Memory-Based Graph Networks (ICLR 2020)
paper 0.7910 ±0.0080 Δ at pub 0.0150
239
SchNet
actual #239 vs paper #250 11 places worse
0.7660 ±0.0110
best reported
actual #239 vs paper #250 11 places worse
paper 0.7500 ±0.0330

Difference within reported uncertainty; not counted as underperformance.

paper 0.7500 ±0.0330 Δ at pub 0.0160
258
MGCN
0.7340 ±0.0300
This paper
261
GREA-GCN
0.7320 ±0.0350
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
10
AMCT
0.9270 ±0.0080
This paper
13
Molformer
actual #13 vs paper #20 7 places worse
0.9260
best reported
actual #13 vs paper #20 7 places worse
paper 0.9180 ±0.0080

Difference within reported uncertainty; not counted as underperformance.

paper 0.9180 ±0.0080 Δ at pub 0.0080
21
Graphormer
actual #21 vs paper #21
0.9170 ±0.0100
actual #21 vs paper #21
paper 0.9170 ±0.0100
paper 0.9170 ±0.0100 Δ at pub 0.2155
34
GIN
0.8875 ±0.0049
38
GCN
actual #38 vs paper #39 1 place worse
0.8810 ±0.0360
best reported
actual #38 vs paper #39 1 place worse
paper 0.8770 ±0.0360

Difference within reported uncertainty; not counted as underperformance.

paper 0.8770 ±0.0360 Δ at pub 0.0040
48
TF-Robust
0.8600 ±0.0870
This paper
52
MGCN
0.8500 ±0.0640
This paper
53
SchNet
actual #53 vs paper #53
0.8480 ±0.0220
best reported
actual #53 vs paper #53
paper 0.8470 ±0.0240

Difference within reported uncertainty; not counted as underperformance.

paper 0.8470 ±0.0240 Δ at pub 0.0010
56
Weave
0.8370 ±0.0650
This paper
61
MGSSL
actual #61 vs paper #128 67 places worse
0.7952 ±0.0198
best reported
actual #61 vs paper #128 67 places worse
paper 0.7050 ±0.0110
69
R-MAT
actual #69 vs paper #69
0.7460
best reported
actual #69 vs paper #69
paper 0.7450 ±0.0100

Difference within reported uncertainty; not counted as underperformance.

paper 0.7450 ±0.0100 Δ at pub 0.0010
76
MAT
0.7370 ±0.0090
This paper
202
GREA-GCN
0.6790 ±0.0180
This paper
#ModelROC-AUC ↑Paper
1
KA-GAT
0.8470 ±0.0020
2
KA-GCN
0.8420 ±0.0010
3
GraphKAN
0.8370 ±0.0010
66
GIN
0.6403 ±0.0104
81
AMCT
0.6330 ±0.0160
This paper
113
MAT
actual #113 vs paper #192 79 places worse
0.6190
best reported
actual #113 vs paper #192 79 places worse
paper 0.5970 ±0.0120
paper 0.5970 ±0.0120 Δ at pub 0.0220
116
MGSSL
actual #116 vs paper #162 46 places worse
0.6180 ±0.0080
best reported
actual #116 vs paper #162 46 places worse
paper 0.6050 ±0.0070

Difference within reported uncertainty; not counted as underperformance.

paper 0.6050 ±0.0070 Δ at pub 0.0130
121
Graphormer
0.6160 ±0.0100
This paper
125
GCN
actual #125 vs paper #196 71 places worse
0.6150 ±0.0250
best reported
actual #125 vs paper #196 71 places worse
paper 0.5930 ±0.0350

Difference within reported uncertainty; not counted as underperformance.

paper 0.5930 ±0.0350 Δ at pub 0.0220
153
TF-Robust
0.6070 ±0.0330
This paper
166
Molformer
0.6050 ±0.0110
This paper
183
R-MAT
0.6000 ±0.0130
This paper
226
GREA-GCN
0.5690 ±0.0230
This paper
232
MGCN
0.5520 ±0.0180
This paper
234
SchNet
actual #234 vs paper #234
0.5450 ±0.0380
actual #234 vs paper #234
paper 0.5450 ±0.0380

Improvement within reported uncertainty; not highlighted.

paper 0.5450 ±0.0380 Δ at pub 0.0060
235
Weave
0.5430 ±0.0340
This paper
#ModelROC-AUC ↑Paper
1
GeomGCL
0.7630
2
LiGhT DeepGPT
0.7570 ±0.0110
3
CoMPT
0.7550
14
GCN
actual #14 vs paper #106 92 places worse
0.7350 ±0.0020
best reported
actual #14 vs paper #106 92 places worse
paper 0.6500 ±0.0250
paper 0.6500 ±0.0250 Δ at pub 0.0850
16
MAT
actual #16 vs paper #60 44 places worse
0.7350
best reported
actual #16 vs paper #60 44 places worse
paper 0.6780 ±0.0090
paper 0.6780 ±0.0090 Δ at pub 0.0570
27
AMCT
0.7150 ±0.0110
This paper
32
GIN
0.7095 ±0.0027
37
Graphormer
0.7030 ±0.0100
This paper
47
Molformer
0.6910 ±0.0120
This paper
52
R-MAT
0.6850 ±0.0090
This paper
60
SchNet
0.6790 ±0.0210
This paper
61
Weave
0.6780 ±0.0240
This paper
84
MGCN
0.6630 ±0.0090
This paper
93
GREA-GCN
0.6580 ±0.0060
This paper
129
MGSSL
actual #129 vs paper #134 5 places worse
0.6410 ±0.0070
best reported
actual #129 vs paper #134 5 places worse
paper 0.6380 ±0.0030

Difference within reported uncertainty; not counted as underperformance.

paper 0.6380 ±0.0030 Δ at pub 0.0030
206
TF-Robust
0.5850 ±0.0310
This paper
#ModelRMSE ↓Paper
1
Graphormer-SPIS
0.4840 ±0.0050
2
Graphormer-SPD
0.4920 ±0.0040
3
conan-FGW
0.5140 ±0.0190
7
GCN
actual #7 vs paper #92 85 places worse
0.5640 ±0.0150
best reported
actual #7 vs paper #92 85 places worse
paper 1.0680 ±0.0500
paper 1.0680 ±0.0500 Δ at pub 0.5040
18
GraphSAGE
0.6010 ±0.0080
20
Weave
actual #20 vs paper #108 88 places worse
0.6100 ±0.0700
best reported
actual #20 vs paper #108 88 places worse
paper 1.1580 ±0.0550
best at pub: MoleculeNet (2017)
paper 1.1580 ±0.0550 Δ at pub 0.5480
24
MAT
actual #24 vs paper #59 35 places worse
0.6240
best reported
actual #24 vs paper #59 35 places worse
paper 0.8380 ±0.0140
paper 0.8380 ±0.0140 Δ at pub 0.2140
47
AMCT
0.8150 ±0.0100
This paper
53
Graphormer
0.8290 ±0.0140
This paper
56
R-MAT
0.8330 ±0.0150
This paper
61
Molformer
0.8480 ±0.0130
This paper
68
GREA-GCN
0.8970 ±0.0360
This paper
90
SchNet
actual #90 vs paper #90
1.0450 ±0.0640
actual #90 vs paper #90
paper 1.0450 ±0.0640

Improvement within reported uncertainty; not highlighted.

paper 1.0450 ±0.0640 Δ at pub 0.0050
113
MGSSL
actual #113 vs paper #113
1.1790 ±0.0080
actual #113 vs paper #113
paper 1.1790 ±0.0080
paper 1.1790 ±0.0080 Δ at pub 0.2590
120
MGCN
actual #120 vs paper #120
1.2660 ±0.1470
actual #120 vs paper #120
paper 1.2660 ±0.1470

Improvement within reported uncertainty; not highlighted.

paper 1.2660 ±0.1470 Δ at pub 0.0040
138
TF-Robust
1.7220 ±0.0380
This paper
SOTA performance (not significantly different from the best) Proposed method (this paper) 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 Best today — OK at publication; today's leaderboard best is elsewhere