ICML 2023

A Group Symmetric Stochastic Differential Equation Model for Molecule Multi-modal Pretraining

Shengchao Liu, Weitao Du, Zhiming Ma, Hongyu Guo, Jian Tang

Main figure for A Group Symmetric Stochastic Differential Equation Model for Molecule Multi-modal Pretraining

Abstract

Molecule pretraining has quickly become the go-to schema to boost the performance of AI-based drug discovery. Naturally, molecules can be represented as 2D topological graphs or 3D geometric point clouds. Although most existing pertaining methods focus on merely the single modality, recent research has shown that maximizing the mutual information (MI) between such two modalities enhances the molecule representation ability. Meanwhile, existing molecule multi-modal pretraining approaches approximate MI based on the representation space encoded from the topology and geometry, thus resulting in the loss of critical structural information of molecules. To address this issue, we propose MoleculeSDE. MoleculeSDE leverages group symmetric (e.g., SE(3)-equivariant and reflection-antisymmetric) stochastic differential equation models to generate the 3D geometries from 2D topologies, and vice versa, directly in the input space. It not only obtains tighter MI bound but also enables prosperous downstream tasks than the previous work. By comparing with 17 pretraining baselines, we empirically verify that MoleculeSDE can learn an expressive representation with state-of-the-art performance on 26 out of 32 downstream tasks.

Benchmark Results

Tested on 7 datasets 17 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
46
ContextPred
actual #46 vs paper #259 213 places worse
0.8060 ±0.0120
best reported
actual #46 vs paper #259 213 places worse
paper 0.7420 ±0.0006
paper 0.7420 ±0.0006 Δ at pub 0.0640
48
3D Infomax
actual #48 vs paper #179 131 places worse
0.8050 ±0.0320
best reported
actual #48 vs paper #179 131 places worse
paper 0.7610 ±0.0018

Difference within reported uncertainty; not counted as underperformance.

paper 0.7610 ±0.0018 Δ at pub 0.0440
61
GraphMVP
actual #61 vs paper #179 118 places worse
0.7990 ±0.0180
best reported
actual #61 vs paper #179 118 places worse
paper 0.7620 ±0.0038
paper 0.7620 ±0.0038 Δ at pub 0.0370
67
MolCLR
actual #67 vs paper #282 215 places worse
0.7980 ±0.0070
best reported
actual #67 vs paper #282 215 places worse
paper 0.7300 ±0.0016
81
InfoGraph
actual #81 vs paper #279 198 places worse
0.7930
best reported
actual #81 vs paper #279 198 places worse
paper 0.7320 ±0.0043
paper 0.7320 ±0.0043 Δ at pub 0.0610
161
MoleculeSDE
0.7680 ±0.0034
This paper
197
SDE (MoleculeSDE)
0.7560
This paper
216
-- (random init)
0.7530 ±0.0022
This paper
229
AttrMask
actual #229 vs paper #238 9 places worse
0.7480 ±0.0025
actual #229 vs paper #238 9 places worse
paper 0.7480 ±0.0025

Improvement within reported uncertainty; not highlighted.

paper 0.7480 ±0.0025 Δ at pub 0.0060
270
VRR (GraphMVP)
0.7360
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 #270 261 places worse
0.8900 ±0.0030
best reported
actual #9 vs paper #270 261 places worse
paper 0.7150 ±0.0317
43
GIN
actual #43 vs paper #239 196 places worse
0.8646 ±0.0081
best reported
actual #43 vs paper #239 196 places worse
paper 0.7650 ±0.0296
paper 0.7650 ±0.0296 Δ at pub 0.0960 Δ today 0.0996
64
GCN
0.8540 ±0.0110
149
GraphMVP
actual #149 vs paper #179 30 places worse
0.8120 ±0.0090
best reported
actual #149 vs paper #179 30 places worse
paper 0.7980 ±0.0074

Difference within reported uncertainty; not counted as underperformance.

paper 0.7980 ±0.0074 Δ at pub 0.0140 Δ today 0.0140
170
MoleculeSDE
0.8040 ±0.0092
This paper
182
AttrMask
actual #182 vs paper #182
0.7970 ±0.0033
actual #182 vs paper #182
paper 0.7970 ±0.0033

Improvement within reported uncertainty; not highlighted.

paper 0.7970 ±0.0033 Δ at pub 0.0250
183
3D Infomax
0.7970 ±0.0154
This paper
186
ContextPred
actual #186 vs paper #242 56 places worse
0.7960 ±0.0120
best reported
actual #186 vs paper #242 56 places worse
paper 0.7600 ±0.0208

Difference within reported uncertainty; not counted as underperformance.

paper 0.7600 ±0.0208 Δ at pub 0.0260 Δ today 0.0360
204
InfoGraph
actual #204 vs paper #223 19 places worse
0.7890 ±0.0110
best reported
actual #204 vs paper #223 19 places worse
paper 0.7780 ±0.0088

Difference within reported uncertainty; not counted as underperformance.

paper 0.7780 ±0.0088 Δ at pub 0.0110
209
SchNet (MoleculeSDE)
0.7860 ±0.0040
This paper
237
-- (random init)
0.7670 ±0.0251
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
34
GIN
0.8875 ±0.0049
40
ContextPred
actual #40 vs paper #259 219 places worse
0.8770 ±0.0260
best reported
actual #40 vs paper #259 219 places worse
paper 0.6570 ±0.0062
paper 0.6570 ±0.0062 Δ at pub 0.2200
41
3D Infomax
actual #41 vs paper #196 155 places worse
0.8770 ±0.0140
best reported
actual #41 vs paper #196 155 places worse
paper 0.6830 ±0.0112
paper 0.6830 ±0.0112 Δ at pub 0.1940
49
GraphMVP
actual #49 vs paper #167 118 places worse
0.8600 ±0.0340
best reported
actual #49 vs paper #167 118 places worse
paper 0.6940 ±0.0021
paper 0.6940 ±0.0021 Δ at pub 0.1660
78
MolCLR
actual #78 vs paper #241 163 places worse
0.7360 ±0.0050
best reported
actual #78 vs paper #241 163 places worse
paper 0.6660 ±0.0189
80
MoleculeSDE
0.7320 ±0.0048
This paper
141
AttrMask
actual #141 vs paper #269 128 places worse
0.7020 ±0.0050
best reported
actual #141 vs paper #269 128 places worse
paper 0.6500 ±0.0236

Difference within reported uncertainty; not counted as underperformance.

paper 0.6500 ±0.0236 Δ at pub 0.0520 Δ today 0.0520
173
InfoGraph
actual #173 vs paper #219 46 places worse
0.6920 ±0.0080
best reported
actual #173 vs paper #219 46 places worse
paper 0.6750 ±0.0011
paper 0.6750 ±0.0011 Δ at pub 0.0170 Δ today 0.0170
200
random init
0.6810 ±0.0059
This paper
#ModelROC-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
12
MolCLR
actual #12 vs paper #50 38 places worse
0.9320 ±0.0170
best reported
actual #12 vs paper #50 38 places worse
paper 0.8610 ±0.0095
19
GCN
0.9130 ±0.0170
40
AttrMask
actual #40 vs paper #40
0.8770 ±0.0119
actual #40 vs paper #40
paper 0.8770 ±0.0119

Improvement within reported uncertainty; not highlighted.

paper 0.8770 ±0.0119 Δ at pub 0.1910
46
MoleculeSDE
0.8700 ±0.0053
This paper
49
GraphMVP
actual #49 vs paper #49
0.8650 ±0.0170
actual #49 vs paper #49
paper 0.8650 ±0.0170
paper 0.8650 ±0.0170 Δ at pub 0.0750
89
3D Infomax
0.7990 ±0.0349
This paper
106
InfoGraph
actual #106 vs paper #117 11 places worse
0.7810
best reported
actual #106 vs paper #117 11 places worse
paper 0.7650 ±0.0107

Difference within reported uncertainty; not counted as underperformance.

paper 0.7650 ±0.0107 Δ at pub 0.0160
115
ContextPred
actual #115 vs paper #115
0.7720 ±0.0088
actual #115 vs paper #115
paper 0.7720 ±0.0088

Improvement within reported uncertainty; not highlighted.

paper 0.7720 ±0.0088 Δ at pub 0.0350
#ModelROC-AUC ↑Paper
1
KA-GAT
0.8470 ±0.0020
2
KA-GCN
0.8420 ±0.0010
3
GraphKAN
0.8370 ±0.0010
14
MolCLR
actual #14 vs paper #219 205 places worse
0.6800 ±0.0110
best reported
actual #14 vs paper #219 205 places worse
paper 0.5750 ±0.0177
66
GIN
actual #66 vs paper #206 140 places worse
0.6403 ±0.0104
best reported
actual #66 vs paper #206 140 places worse
paper 0.5840 ±0.0050
70
GraphMVP
actual #70 vs paper #162 92 places worse
0.6390 ±0.0120
best reported
actual #70 vs paper #162 92 places worse
paper 0.6050 ±0.0025
103
ContextPred
actual #103 vs paper #103
0.6220 ±0.0059
actual #103 vs paper #103
paper 0.6220 ±0.0059

Improvement within reported uncertainty; not highlighted.

paper 0.6220 ±0.0059 Δ at pub 0.0130
125
GCN
0.6150 ±0.0250
134
AttrMask
actual #134 vs paper #134
0.6120 ±0.0012
actual #134 vs paper #134
paper 0.6120 ±0.0012

Improvement within reported uncertainty; not highlighted.

paper 0.6120 ±0.0012 Δ at pub 0.0080
148
MoleculeSDE
0.6080 ±0.0039
This paper
155
3D Infomax
actual #155 vs paper #155
0.6060 ±0.0078
actual #155 vs paper #155
paper 0.6060 ±0.0078

Improvement within reported uncertainty; not highlighted.

paper 0.6060 ±0.0078 Δ at pub 0.0210
162
InfoGraph
actual #162 vs paper #183 21 places worse
0.5990 ±0.0030
actual #162 vs paper #183 21 places worse
paper 0.5990 ±0.0030

Improvement within reported uncertainty; not highlighted.

paper 0.5990 ±0.0030 Δ at pub 0.0050
165
SchNet with MoleculeSDE
0.6050 ±0.0039
This paper
179
SchNet with ConfGF
0.6010 ±0.0087
This paper
196
SchNet with MMFF
0.5940 ±0.0027
This paper
230
SchNet with ClofNet
0.5600 ±0.0010
This paper
#ModelROC-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
actual #25 vs paper #110 85 places worse
0.7160 ±0.0130
best reported
actual #25 vs paper #110 85 places worse
paper 0.6480 ±0.0025
paper 0.6480 ±0.0025 Δ at pub 0.0680
28
ContextPred
actual #28 vs paper #177 149 places worse
0.7140 ±0.0180
best reported
actual #28 vs paper #177 149 places worse
paper 0.6250 ±0.0031
paper 0.6250 ±0.0031 Δ at pub 0.0890
35
InfoGraph
actual #35 vs paper #135 100 places worse
0.7050
best reported
actual #35 vs paper #135 100 places worse
paper 0.6370 ±0.0050
paper 0.6370 ±0.0050 Δ at pub 0.0680
50
GraphMVP
actual #50 vs paper #113 63 places worse
0.6890 ±0.0100
best reported
actual #50 vs paper #113 63 places worse
paper 0.6450 ±0.0020
paper 0.6450 ±0.0020 Δ at pub 0.0440
103
MoleculeSDE
0.6520 ±0.0031
This paper
150
AttrMask
actual #150 vs paper #165 15 places worse
0.6290 ±0.0011
actual #150 vs paper #165 15 places worse
paper 0.6290 ±0.0011

Improvement within reported uncertainty; not highlighted.

paper 0.6290 ±0.0011 Δ at pub 0.0040
166
MolCLR
0.6290 ±0.0038
This paper

Quantum Chemistry

#ModelMAE ↓Paper
1
QHNet
0.0000
2
QHNetV2
0.0000
3
PhiSNet
0.0000
104
MoleculeSDE
actual #104 vs paper #114 10 places worse
0.2820
best reported
actual #104 vs paper #114 10 places worse
paper 1.1120
108
random init
0.3800
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