├── LICENSE
├── README.md
├── environment_gpu.yml
├── model
├── modelc.pth
└── modelp.pth
├── result
└── predict_test2016.csv
├── src
├── dataset.py
├── metrics.py
├── model.py
├── predict.py
└── train.py
└── test_set
├── Vina_terms13851.pkl
├── Vina_terms2013.pkl
├── Vina_terms2016.pkl
├── labels_test2013.csv
├── labels_test2016.csv
├── labels_train13851.csv
├── train_valte_comp.pkl
└── train_valte_prot.pkl
/LICENSE:
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573 | option of following the terms and conditions either of that numbered
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575 | Foundation. If the Program does not specify a version number of the
576 | GNU General Public License, you may choose any version ever published
577 | by the Free Software Foundation.
578 |
579 | If the Program specifies that a proxy can decide which future
580 | versions of the GNU General Public License can be used, that proxy's
581 | public statement of acceptance of a version permanently authorizes you
582 | to choose that version for the Program.
583 |
584 | Later license versions may give you additional or different
585 | permissions. However, no additional obligations are imposed on any
586 | author or copyright holder as a result of your choosing to follow a
587 | later version.
588 |
589 | 15. Disclaimer of Warranty.
590 |
591 | THERE IS NO WARRANTY FOR THE PROGRAM, TO THE EXTENT PERMITTED BY
592 | APPLICABLE LAW. EXCEPT WHEN OTHERWISE STATED IN WRITING THE COPYRIGHT
593 | HOLDERS AND/OR OTHER PARTIES PROVIDE THE PROGRAM "AS IS" WITHOUT WARRANTY
594 | OF ANY KIND, EITHER EXPRESSED OR IMPLIED, INCLUDING, BUT NOT LIMITED TO,
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610 | SUCH DAMAGES.
611 |
612 | 17. Interpretation of Sections 15 and 16.
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614 | If the disclaimer of warranty and limitation of liability provided
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619 | copy of the Program in return for a fee.
620 |
621 | END OF TERMS AND CONDITIONS
622 |
623 | How to Apply These Terms to Your New Programs
624 |
625 | If you develop a new program, and you want it to be of the greatest
626 | possible use to the public, the best way to achieve this is to make it
627 | free software which everyone can redistribute and change under these terms.
628 |
629 | To do so, attach the following notices to the program. It is safest
630 | to attach them to the start of each source file to most effectively
631 | state the exclusion of warranty; and each file should have at least
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633 |
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635 | Copyright (C)
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637 | This program is free software: you can redistribute it and/or modify
638 | it under the terms of the GNU General Public License as published by
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642 | This program is distributed in the hope that it will be useful,
643 | but WITHOUT ANY WARRANTY; without even the implied warranty of
644 | MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the
645 | GNU General Public License for more details.
646 |
647 | You should have received a copy of the GNU General Public License
648 | along with this program. If not, see .
649 |
650 | Also add information on how to contact you by electronic and paper mail.
651 |
652 | If the program does terminal interaction, make it output a short
653 | notice like this when it starts in an interactive mode:
654 |
655 | Copyright (C)
656 | This program comes with ABSOLUTELY NO WARRANTY; for details type `show w'.
657 | This is free software, and you are welcome to redistribute it
658 | under certain conditions; type `show c' for details.
659 |
660 | The hypothetical commands `show w' and `show c' should show the appropriate
661 | parts of the General Public License. Of course, your program's commands
662 | might be different; for a GUI interface, you would use an "about box".
663 |
664 | You should also get your employer (if you work as a programmer) or school,
665 | if any, to sign a "copyright disclaimer" for the program, if necessary.
666 | For more information on this, and how to apply and follow the GNU GPL, see
667 | .
668 |
669 | The GNU General Public License does not permit incorporating your program
670 | into proprietary programs. If your program is a subroutine library, you
671 | may consider it more useful to permit linking proprietary applications with
672 | the library. If this is what you want to do, use the GNU Lesser General
673 | Public License instead of this License. But first, please read
674 | .
675 |
--------------------------------------------------------------------------------
/README.md:
--------------------------------------------------------------------------------
1 | ## About GraphscoreDTA
2 |
3 | GraphscoreDTA is an optimized graph neural network for protein-ligand binding affinity prediction.
4 |
5 | The benchmark dataset can be found in `./test_set/`. The GraphscoreDTA model is available in `./src/`. And the result will be generated in `./result/`. See our paper for more details.
6 |
7 | **[IMPORTANT] We provide the input file in the [release page](https://github.com/CSUBioGroup/GraphscoreDTA/releases/tag/Data).** Please download it to `./test_set/`.
8 |
9 | ### Requirements:
10 | - python 3.7.11
11 | - pytorch 1.9.0
12 | - scikit-learn 0.24.2
13 | - dgl 0.9.1.post1
14 | - tqdm 4.62.2
15 | - ipython 7.27.0
16 | - numpy 1.20.3
17 | - pandas 1.3.2
18 | - numba 0.53.1
19 | - scipy 1.7.1
20 |
21 | ### Installation
22 |
23 | In order to get GraphscoreDTA, you need to clone this repo:
24 |
25 | ```bash
26 | git clone https://github.com/CSUBioGroup/GraphscoreDTA
27 | cd GraphscoreDTA
28 | ```
29 | The easiest way to install the required packages is to create environment with GPU-enabled version:
30 | ```bash
31 | conda env create -f environment_gpu.yml
32 | conda activate GraphscoreDTA
33 | ```
34 | ### Predict
35 |
36 | to use our model
37 | ```bash
38 | cd ./src/
39 | python predict.py
40 | ```
41 |
42 | ### Training
43 |
44 | to train your own model
45 | ```bash
46 | cd ./src/
47 | python train.py
48 | ```
49 |
50 | ## Citation
51 | Wang K, Zhou R, Tang J, et al. GraphscoreDTA: optimized graph neural network for protein–ligand binding affinity prediction[J]. Bioinformatics, 2023, 39(6): btad340.
52 |
53 | ## Contact
54 | Kaili Wang: [kailiwang@dhu.edu.cn](mailto:kailiwang@dhu.edu.cn)
55 |
56 | You can also download the codes from https://github.com/KailiWang1/GraphscoreDTA
57 |
--------------------------------------------------------------------------------
/environment_gpu.yml:
--------------------------------------------------------------------------------
1 | name: GraphscoreDTA
2 | channels:
3 | - pytorch
4 | - pypi
5 | - dglteam
6 | - defaults
7 | dependencies:
8 | - python=3.7.11
9 | - pytorch=1.9.0
10 | - scikit-learn=0.24.2
11 | - dgl-cuda10.2
12 | - tqdm=4.62.2
13 | - ipython=7.27.0
14 | - numpy=1.20.3
15 | - pandas=1.3.2
16 | - numba=0.53.1
17 | - scipy=1.7.1
--------------------------------------------------------------------------------
/model/modelc.pth:
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https://raw.githubusercontent.com/CSUBioGroup/GraphscoreDTA/d7d1230fb33d803f5c8f86e66c1598ab4d7ea68d/model/modelc.pth
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/model/modelp.pth:
--------------------------------------------------------------------------------
https://raw.githubusercontent.com/CSUBioGroup/GraphscoreDTA/d7d1230fb33d803f5c8f86e66c1598ab4d7ea68d/model/modelp.pth
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/result/predict_test2016.csv:
--------------------------------------------------------------------------------
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255 | 253,2vkm,9.193043,8.74,test2016
256 | 254,4agn,5.050665,3.97,test2016
257 | 255,3kr8,7.4719357,8.1,test2016
258 | 256,4qac,9.012026,9.4,test2016
259 | 257,4owm,4.0151052,2.96,test2016
260 | 258,3arq,6.394947,6.4,test2016
261 | 259,2zb1,7.891885,6.32,test2016
262 | 260,3g2z,3.2193325,2.36,test2016
263 | 261,4hge,8.539055,7.92,test2016
264 | 262,4twp,7.186953,10.0,test2016
265 | 263,2w4x,5.172502,4.85,test2016
266 | 264,3wz8,6.919074,5.82,test2016
267 | 265,3fv2,7.5154085,8.11,test2016
268 | 266,1lpg,8.856076,7.09,test2016
269 | 267,3nw9,8.7463875,9.0,test2016
270 | 268,4llx,4.46778,2.89,test2016
271 | 269,4eo8,7.170371,8.15,test2016
272 | 270,3nx7,7.09548,8.1,test2016
273 | 271,1y6r,9.657782,10.11,test2016
274 | 272,4ty7,8.774184,9.52,test2016
275 | 273,3b68,9.309081,8.4,test2016
276 | 274,2al5,6.62235,8.4,test2016
277 | 275,2qe4,8.151821,7.96,test2016
278 | 276,4x6p,10.029287,8.3,test2016
279 | 277,2v00,3.4644861,3.66,test2016
280 | 278,3zt2,6.388214,2.84,test2016
281 |
--------------------------------------------------------------------------------
/src/dataset.py:
--------------------------------------------------------------------------------
1 | from torch.utils.data import Dataset
2 | import numpy as np
3 | import dgl
4 | import torch
5 |
6 | class WholeDataset(Dataset):
7 | def __init__(self, graphs, vina, labels, affinities):
8 | self.graphs = graphs
9 | self.vina = vina
10 | self.labels = labels
11 | self.affinities = affinities
12 | self.length = len(labels)
13 |
14 | def __getitem__(self, index: int):
15 | return (self.graphs[index], self.vina[index], self.affinities[index])
16 |
17 | def get_name(self, index):
18 | return self.labels[index]
19 |
20 | def __len__(self) -> int:
21 | return self.length
22 |
23 | class SepDataset(WholeDataset):
24 | def __init__(self, graphs, vina, labels, affinities, edge_types):
25 | super().__init__(graphs, vina, labels, affinities)
26 | self.edge_types = edge_types
27 | def __getitem__(self, index: int):
28 | g = self.graphs[index]
29 | sub_gs = [g.edge_type_subgraph((i,)) for i in self.edge_types]
30 | return (*sub_gs, self.vina[index], self.affinities[index], self.labels[index])
31 |
32 | def collate_fn(data):
33 | *gs, vina, labels, idlist = zip(*data)
34 | vina_list = []
35 | for vina_i in vina:
36 | vina_list.append(list(vina_i))
37 | vina = np.array(vina_list)
38 | labels = torch.tensor(labels)
39 | vina = torch.tensor(vina)
40 | gs = [dgl.batch(i) for i in gs]
41 |
42 | return gs+ [labels.float()], vina, idlist
43 |
--------------------------------------------------------------------------------
/src/metrics.py:
--------------------------------------------------------------------------------
1 | import numpy as np
2 | import sklearn.metrics as m
3 | from scipy.stats import pearsonr
4 | from numba import njit
5 |
6 | @njit
7 | def c_index(y_true, y_pred):
8 | summ = 0
9 | pair = 0
10 |
11 | for i in range(1, len(y_true)):
12 | for j in range(0, i):
13 | pair += 1
14 | if y_true[i] > y_true[j]:
15 | summ += 1 * (y_pred[i] > y_pred[j]) + 0.5 * (y_pred[i] == y_pred[j])
16 | elif y_true[i] < y_true[j]:
17 | summ += 1 * (y_pred[i] < y_pred[j]) + 0.5 * (y_pred[i] == y_pred[j])
18 | else:
19 | pair -= 1
20 | if pair != 0:
21 | return summ / pair
22 | else:
23 | return 0
24 |
25 | def RMSE(y_true, y_pred):
26 | return np.sqrt(m.mean_squared_error(y_true, y_pred))
27 |
28 | def MAE(y_true, y_pred):
29 | return m.mean_absolute_error(y_true, y_pred)
30 |
31 | def CORR(y_true, y_pred):
32 | return pearsonr(y_true, y_pred)[0]
33 |
34 | def SD(y_true, y_pred):
35 | from sklearn.linear_model import LinearRegression
36 | y_pred = y_pred.reshape((-1,1))
37 | lr = LinearRegression().fit(y_pred,y_true)
38 | y_ = lr.predict(y_pred)
39 | return np.sqrt(np.square(y_true - y_).sum() / (len(y_pred) - 1))
40 |
--------------------------------------------------------------------------------
/src/model.py:
--------------------------------------------------------------------------------
1 | import dgl
2 | import dgl.function as dglfn
3 | import dgl.nn.pytorch as dglnn
4 | import numpy as np
5 | import torch
6 | import torch.nn as nn
7 | import torch.nn.functional as F
8 |
9 |
10 | class ModelNew(nn.Module):
11 |
12 | def __init__(self):
13 | super().__init__()
14 | self.a_init = nn.Linear(82, 120)
15 | self.b_init = nn.Linear(12, 8)
16 | self.r_init_1 = nn.Linear(20, 9)
17 | self.r_init_2 = nn.Linear(9 + 21, 120)
18 | # message transport
19 | self.r_mt = MT(120)
20 | self.a_mt = MT(120)
21 | # ligand
22 | self.A = nn.Linear(120, 120)
23 | self.B = nn.Linear(120*2,120)
24 | self.a_conv1 = SConv1(120, 8, 120, 4)
25 | self.a_conv2 = SConv1(120, 8, 120, 4)
26 | # protein
27 | self.C = nn.Linear(120, 120)
28 | self.D = nn.Linear(120*2,120)
29 | self.r_conv1 = SConvr1(120, 0, 120, 4)
30 | self.r_conv2 = SConvr1(120, 0, 120, 4)
31 | # interaction
32 | self.i_conf = DistanceConv(120, 8, 3)
33 | # predict
34 | self.classifier = nn.Sequential(
35 | nn.Linear(120 + 120 + 120 + 6, 298),
36 | nn.PReLU(),
37 | nn.Linear(298, 160),
38 | nn.PReLU(),
39 | nn.Linear(160, 1)
40 | )
41 |
42 | self.sum_pool = dglnn.SumPooling()
43 | self.mean_pool = dglnn.AvgPooling()
44 |
45 | def forward(self, ga, gr, gi, vina):
46 | device = torch.device("cuda:0")
47 | ga = ga.to('cuda:0')
48 | gr = gr.to('cuda:0')
49 | gi = gi.to('cuda:0')
50 | vina = vina.to('cuda:0')
51 |
52 | va_init = self.a_init(ga.ndata['feat'])
53 | ea = self.b_init(ga.edata['feat'])
54 | vr = self.r_init_1(gr.ndata['feat'][:, :20])
55 | vr = torch.cat((vr, gr.ndata['feat'][:, 20:]), -1)
56 | vr_init = self.r_init_2(vr)
57 |
58 | vi_a = self.a_init(gi.ndata['feat']['atom'])
59 | vi_r = self.r_init_1(gi.ndata['feat']['residue'][:, :20])
60 | vi_r = torch.cat((vi_r, gi.ndata['feat']['residue'][:, 20:]), -1)
61 | vi_r = self.r_init_2(vi_r)
62 | vi_init = torch.cat((vi_a, vi_r), dim=0)
63 | ei = gi.edata['weight'].reshape(-1)
64 | ei = torch.cat((ei, ei)).unsqueeze(1)
65 |
66 | gii = dgl.add_reverse_edges(dgl.to_homogeneous(gi))
67 | gii.set_batch_num_nodes(gi.batch_num_nodes('atom') + gi.batch_num_nodes('residue'))
68 | gii.set_batch_num_edges(gi.batch_num_edges() * 2)
69 | va = self.a_mt(gr, vr_init, ga, va_init)
70 | vr = self.r_mt(ga, va_init, gr, vr_init)
71 | # ligand
72 | va = F.leaky_relu(self.A(va), 0.1)
73 | sa = self.sum_pool(ga, va)
74 | va, sa = self.a_conv1(ga, va, ea, sa)
75 | va, sa = self.a_conv2(ga, va+va_init, ea, sa)
76 | fa = torch.cat((self.mean_pool(ga, va), sa), dim=-1)
77 | fa = self.B(fa)
78 | fa = fa + self.mean_pool(ga,va_init)
79 | vr = F.leaky_relu(self.C(vr), 0.1)
80 | sr = self.sum_pool(gr, vr)
81 | vr, sr = self.r_conv1(gr, vr, torch.Tensor().reshape(gr.num_edges(),-1).to(device), sr)
82 | vr, sr = self.r_conv2(gr, vr+vr_init, torch.Tensor().reshape(gr.num_edges(),-1).to(device), sr)
83 | fr = torch.cat((self.mean_pool(gr, vr), sr), dim=-1)
84 | fr = self.D(fr)
85 | fr = fr + self.mean_pool(gr,vr_init)
86 | # interaction
87 | vi = self.i_conf(gii, vi_init, ei)
88 | vi = vi + vi_init
89 |
90 | fi = self.mean_pool(gii, vi)
91 | f = torch.cat((fa, fr, fi, vina), dim=-1)
92 | y = self.classifier(f)
93 |
94 | return y
95 |
96 | class MT(nn.Module):
97 |
98 | def __init__(self, in_dim):
99 | super().__init__()
100 |
101 | self.A = nn.Linear(in_dim, 64)
102 | self.B = nn.Linear(in_dim, 8)
103 | self.C = nn.Linear(64, in_dim)
104 | self.sum_pool = dglnn.SumPooling()
105 | self.D = nn.Linear(in_dim, 120)
106 | self.E = nn.Linear(in_dim, 120)
107 |
108 | def forward(self, ga, va, gb, vb):
109 | s = self.A(va)
110 | h = self.B(va)
111 | with ga.local_scope():
112 | ga.ndata['h'] = h
113 | h = dgl.softmax_nodes(ga, 'h')
114 | ga.ndata['h'] = h
115 | ga.ndata['s'] = s
116 | gga = dgl.unbatch(ga)
117 | gp_ = torch.stack([torch.mm(g.ndata['s'].T, g.ndata['h']) for g in gga])
118 | gp_ = self.C(gp_.mean(dim=-1))
119 |
120 | gp2_ = self.D(gp_)
121 | gp3_ = dgl.broadcast_nodes(gb, gp2_)
122 | gp3_ = gp3_.permute(1,0)
123 | r_ = torch.sum(torch.mm(self.E(vb),gp3_),dim=-1)
124 | pad_ = torch.sigmoid(r_)
125 | vbb = vb + vb * pad_.unsqueeze(1)
126 |
127 | return vbb
128 |
129 | class SConv1(nn.Module):
130 | def __init__(self, v_dim, e_dim, h_dim, k_head):
131 | super().__init__()
132 |
133 | self.A = nn.Linear(v_dim, h_dim)
134 | self.m2s = nn.ModuleList([SConv1.Helper(v_dim, h_dim) for _ in range(k_head)])
135 | self.B = nn.Linear(h_dim * k_head, h_dim)
136 | self.C = nn.Linear(v_dim, h_dim)
137 | self.D = nn.Linear(e_dim + v_dim, h_dim)
138 | self.E = nn.Linear(h_dim + v_dim, h_dim)
139 | self.K = nn.Linear(e_dim, h_dim)
140 | self.gate_update_m = SConv1.GateUpdate(h_dim)
141 | self.gate_update_s = SConv1.GateUpdate(h_dim)
142 |
143 | def __msg_func(self, edges):
144 | v = edges.src['v']
145 | e = edges.data['e']
146 |
147 | return {'ve': F.leaky_relu(self.K(e) * v,0.1)}
148 |
149 | def forward(self, g, v, e, s):
150 | s2s = torch.tanh(self.A(s))
151 | m2s = torch.cat([layer(g, v, s) for layer in self.m2s],dim=1)
152 | m2s = torch.tanh(self.B(m2s))
153 | s2m = torch.tanh(self.C(s))
154 | s2m = dgl.broadcast_nodes(g, s2m)
155 |
156 | with g.local_scope():
157 | g.ndata['v'] = v
158 | g.edata['e'] = e
159 | g.update_all(self.__msg_func, dglfn.sum('ve', 'sve'))
160 | svev = torch.cat((g.ndata['sve'], v),dim=1)
161 | m2m = F.leaky_relu(self.E(svev), 0.1 )
162 | vv = self.gate_update_m(m2m, s2m, v)
163 | ss = self.gate_update_s(s2s, m2s, s)
164 |
165 | return vv, ss
166 |
167 | class Helper(nn.Module):
168 | def __init__(self, v_dim, h_dim):
169 | super().__init__()
170 |
171 | self.A = nn.Linear(v_dim, h_dim)
172 | self.B = nn.Linear(v_dim, h_dim)
173 | self.C = nn.Linear(h_dim, 1)
174 | self.D = nn.Linear(v_dim, h_dim)
175 |
176 | def forward(self, g, v, s):
177 | d_node = torch.tanh(self.A(v))
178 | d_super = torch.tanh(self.B(s))
179 | d_super = dgl.broadcast_nodes(g, d_super)
180 |
181 | a = self.C(d_node * d_super).reshape(-1)
182 |
183 | with g.local_scope():
184 | g.ndata['a'] = a
185 | a = dgl.softmax_nodes(g, 'a')
186 |
187 | g.ndata['h'] = self.D(v) * a.unsqueeze(1)
188 | main2super_i = dgl.sum_nodes(g, 'h')
189 |
190 | return main2super_i
191 |
192 | class GateUpdate(nn.Module):
193 |
194 | def __init__(self, h_dim):
195 | super().__init__()
196 |
197 | self.A = nn.Linear(h_dim, h_dim)
198 | self.B = nn.Linear(h_dim, h_dim)
199 | self.gru = nn.GRUCell(h_dim, h_dim)
200 |
201 | def forward(self, a, b, c):
202 | z = torch.sigmoid(self.A(a) + self.B(b))
203 | h = z * b + (1 - z) * a
204 | cc = self.gru(c, h)
205 | return cc
206 |
207 | class SConvr1(nn.Module):
208 | def __init__(self, v_dim, e_dim, h_dim, k_head):
209 | super().__init__()
210 |
211 | self.A = nn.Linear(v_dim, h_dim)
212 | self.m2s = nn.ModuleList([SConvr1.Helper(v_dim, h_dim) for _ in range(k_head)])
213 | self.B = nn.Linear(h_dim * k_head, h_dim)
214 | self.C = nn.Linear(v_dim, h_dim)
215 | self.D = nn.Linear(e_dim + v_dim, h_dim)
216 | self.E = nn.Linear(h_dim + v_dim, h_dim)
217 | self.gate_update_m = SConvr1.GateUpdate(h_dim)
218 | self.gate_update_s = SConvr1.GateUpdate(h_dim)
219 |
220 | def __msg_func(self, edges):
221 | v = edges.src['v']
222 | e = edges.data['e']
223 | return {'ve': F.leaky_relu(v,0.1)}
224 |
225 | def forward(self, g, v, e, s):
226 | s2s = torch.tanh(self.A(s))
227 | m2s = torch.cat([layer(g, v, s) for layer in self.m2s],dim=1)
228 | m2s = torch.tanh(self.B(m2s))
229 | s2m = torch.tanh(self.C(s))
230 | s2m = dgl.broadcast_nodes(g, s2m)
231 |
232 | with g.local_scope():
233 | g.ndata['v'] = v
234 | g.edata['e'] = e
235 | g.update_all(self.__msg_func, dglfn.sum('ve', 'sve'))
236 | svev = torch.cat((g.ndata['sve'], v),dim=1)
237 | m2m = F.leaky_relu(self.E(svev), 0.1 )
238 | vv = self.gate_update_m(m2m, s2m, v)
239 | ss = self.gate_update_s(s2s, m2s, s)
240 |
241 | return vv, ss
242 |
243 | class Helper(nn.Module):
244 | def __init__(self, v_dim, h_dim):
245 | super().__init__()
246 | self.A = nn.Linear(v_dim, h_dim)
247 | self.B = nn.Linear(v_dim, h_dim)
248 | self.C = nn.Linear(h_dim, 1)
249 | self.D = nn.Linear(v_dim, h_dim)
250 |
251 | def forward(self, g, v, s):
252 | d_node = torch.tanh(self.A(v))
253 | d_super = torch.tanh(self.B(s))
254 | d_super = dgl.broadcast_nodes(g, d_super)
255 | a = self.C(d_node * d_super).reshape(-1)
256 |
257 | with g.local_scope():
258 | g.ndata['a'] = a
259 | a = dgl.softmax_nodes(g, 'a')
260 | g.ndata['h'] = self.D(v) * a.unsqueeze(1)
261 | main2super_i = dgl.sum_nodes(g, 'h')
262 |
263 | return main2super_i
264 |
265 | class GateUpdate(nn.Module):
266 | def __init__(self, h_dim):
267 | super().__init__()
268 | self.A = nn.Linear(h_dim, h_dim)
269 | self.B = nn.Linear(h_dim, h_dim)
270 | self.gru = nn.GRUCell(h_dim, h_dim)
271 |
272 | def forward(self, a, b, c):
273 | z = torch.sigmoid(self.A(a) + self.B(b))
274 | h = z * b + (1 - z) * a
275 | cc = self.gru(c, h)
276 | return cc
277 |
278 | class DistanceConv(nn.Module):
279 |
280 | def __init__(self, dim, rc, depth):
281 | super().__init__()
282 | self.rs = nn.Parameter(torch.rand(1))
283 | self.sigma = nn.Parameter(torch.rand(1))
284 | self.A = nn.Linear(dim, dim)
285 | self.rc = rc
286 | self.depth = depth
287 |
288 | def f(self, r):
289 | return torch.exp((-torch.square(r - self.rs) / torch.square(self.sigma))) * \
290 | 0.5 * torch.cos(np.pi * r / self.rc) * (r < self.rc)
291 |
292 | def __msg_func(self, edges):
293 | v = edges.src['v']
294 | f = edges.data['f']
295 | return {'vf': f * v}
296 |
297 | def forward(self, g, v, e):
298 | with g.local_scope():
299 | g.ndata['v'] = v
300 | g.edata['f'] = self.f(e)
301 | for _ in range(self.depth):
302 | g.update_all(self.__msg_func, dglfn.sum('vf', 'svf'))
303 | g.ndata['v'] = torch.relu(self.A(g.ndata['svf']+v))
304 | v = g.ndata['v']
305 |
306 | return v
307 |
--------------------------------------------------------------------------------
/src/predict.py:
--------------------------------------------------------------------------------
1 | import sys
2 | import time
3 | from datetime import datetime
4 | import numpy as np
5 | import pandas as pd
6 | import torch
7 | import torch.nn as nn
8 | import torch.nn.functional as F
9 | from torch.utils.data import DataLoader
10 | # from tqdm import tqdm_notebook as tqdm
11 | import pickle
12 | import random
13 | from sklearn.model_selection import KFold, train_test_split
14 | import dgl
15 | import dgl.nn.pytorch as dglnn
16 | import dgl.function as dglfn
17 | from collections import deque
18 | from tqdm.auto import tqdm
19 | from IPython.display import clear_output
20 |
21 | from dataset import SepDataset, collate_fn
22 | from model import ModelNew
23 | import metrics
24 |
25 | def test(model, valid_loader_compound, criterion,device):
26 | model.eval()
27 | losses = []
28 | outputs = []
29 | targets = []
30 | name_list =[]
31 | tbar = tqdm(valid_loader_compound, total=len(valid_loader_compound))
32 | for i, data in enumerate(tbar):
33 | data0 = [i.to(device) for i in data[0]]
34 | ga, gr, gi, aff = data0
35 | vina = data[1]
36 | idnames = data[2]
37 | name_l = []
38 | for name in idnames:
39 | name_l.append(name)
40 | name_list.append(name_l)
41 | with torch.no_grad():
42 | y_pred = model(ga,gr,gi,vina).squeeze()
43 | y_true = aff.float().squeeze()
44 | assert y_pred.shape == y_true.shape
45 | loss = criterion(y_pred,y_true).cuda()
46 | losses.append(loss.item())
47 | outputs.append(y_pred.cpu().detach().numpy().reshape(-1))
48 | targets.append(y_true.cpu().detach().numpy().reshape(-1))
49 | targets = np.concatenate(targets).reshape(-1)
50 | outputs = np.concatenate(outputs).reshape(-1)
51 | name_list = np.concatenate(name_list).reshape(-1)
52 | evaluation = {
53 | 'c_index': metrics.c_index(targets, outputs),
54 | 'RMSE': metrics.RMSE(targets, outputs),
55 | 'MAE': metrics.MAE(targets, outputs),
56 | 'SD': metrics.SD(targets, outputs),
57 | 'CORR': metrics.CORR(targets, outputs),}
58 |
59 | return evaluation,targets, outputs, name_list
60 |
61 | def main():
62 | flag = 'predict'
63 | model_path = '../model/modelp.pth'
64 | device = torch.device("cuda" if torch.cuda.is_available() else "cpu")
65 | SHOW_PROCESS_BAR = False
66 |
67 | vina_list16 = []
68 | graphs16 = dgl.load_graphs('../test_set/all_in_one_graph_test2016.bin')[0]
69 | labels16 = pd.read_csv('../test_set/labels_test2016.csv')
70 | vina_terms16 =open(r'../test_set/Vina_terms2016.pkl','rb')
71 | vina16 = pickle.load(vina_terms16)
72 | for i in range(279):# number
73 | if labels16.id[i] in vina16.keys():
74 | vina_list16.append(vina16[labels16.id[i]])
75 |
76 | test16_dataset = SepDataset([graphs16[i] for i in range(len(graphs16))], [vina_list16[i] for i in range(len(vina_list16))], [labels16.id[i] for i in range(len(labels16))], [labels16.affinity[i] for i in range(len(labels16))], ['a_conn','r_conn', 'int_l'])
77 | test2016_loader = DataLoader(test16_dataset, batch_size=32, shuffle=False, num_workers=0, collate_fn=collate_fn)
78 |
79 | model = ModelNew()
80 | checkpoint = torch.load(model_path,map_location=device)
81 | model.load_state_dict(checkpoint['model'])
82 | model.to(device)
83 | criterion = torch.nn.MSELoss()
84 | p = test2016_loader
85 | p_f = 'test2016'
86 | print(f'{flag}_{p_f}.csv')
87 | evoluation,targets,outputs,names = test(model, p, criterion,device)
88 | a = pd.DataFrame()
89 | a=a.assign(pdbid=names,predicted=outputs,real=targets,set=p_f)
90 | a.to_csv(f'../result/{flag}_{p_f}.csv')
91 | print(evoluation)
92 | if __name__ == "__main__":
93 | main()
--------------------------------------------------------------------------------
/src/train.py:
--------------------------------------------------------------------------------
1 | import pickle
2 | import random
3 | import pandas as pd
4 | import numpy as np
5 | from sklearn.model_selection import KFold, train_test_split
6 | import torch
7 | import torch.nn as nn
8 | import torch.nn.functional as F
9 | from torch.utils.data import DataLoader
10 | import dgl
11 | import dgl.nn.pytorch as dglnn
12 | import dgl.function as dglfn
13 | from collections import deque
14 | from tqdm.auto import tqdm
15 | from IPython.display import clear_output
16 | import time
17 |
18 | from dataset import SepDataset, collate_fn
19 | from model import ModelNew
20 | import metrics
21 |
22 | seed = np.random.randint(2021, 2022) ##random
23 |
24 | torch.backends.cudnn.deterministic = True
25 | torch.backends.cudnn.benchmark = False
26 |
27 | torch.manual_seed(seed)
28 | np.random.seed(seed)
29 |
30 |
31 | def timeSince(since):
32 | now = time.time()
33 | s = now - since
34 | return now, s
35 |
36 | def train(model, train_loader_compound, criterion, optimizer,epoch,device):
37 | model.train()
38 | tbar = tqdm(train_loader_compound, total=len(train_loader_compound))
39 | losses = []
40 | t = time.time()
41 | for i, data in enumerate(tbar):
42 | data0 = [i.to(device) for i in data[0]]
43 | ga, gr, gi, aff = data0
44 | vina = data[1]
45 | y_pred = model(ga,gr,gi,vina).squeeze()
46 | y_true = aff.float().squeeze()
47 |
48 | assert y_pred.shape == y_true.shape
49 | loss = criterion(y_pred,y_true).cuda()
50 | loss.backward()
51 | grad_norm = torch.nn.utils.clip_grad_norm_(model.parameters(), 5)
52 | optimizer.step()
53 | optimizer.zero_grad()
54 | losses.append(loss.item())
55 | # tbar.set_description(f'epoch {epoch+1} loss {np.mean(losses[-10:]):.4f} grad {grad_norm:.4f}')
56 |
57 | m_losses=np.mean(losses)
58 |
59 | return m_losses
60 |
61 | def valid(model, valid_loader_compound, criterion,device):
62 | model.eval()
63 | losses = []
64 | outputs = []
65 | targets = []
66 | tbar = tqdm(valid_loader_compound, total=len(valid_loader_compound))
67 | for i, data in enumerate(tbar):
68 | data0 = [i.to(device) for i in data[0]]
69 | ga, gr, gi, aff = data0
70 | vina = data[1]
71 | with torch.no_grad():
72 | y_pred = model(ga,gr,gi,vina).squeeze()
73 | y_true = aff.float().squeeze()
74 | assert y_pred.shape == y_true.shape
75 | loss = criterion(y_pred,y_true).cuda()
76 | losses.append(loss.item())
77 | outputs.append(y_pred.cpu().detach().numpy().reshape(-1))
78 | targets.append(y_true.cpu().detach().numpy().reshape(-1))
79 | targets = np.concatenate(targets).reshape(-1)
80 | outputs = np.concatenate(outputs).reshape(-1)
81 |
82 | evaluation = {
83 | 'c_index': metrics.c_index(targets, outputs),
84 | 'RMSE': metrics.RMSE(targets, outputs),
85 | 'MAE': metrics.MAE(targets, outputs),
86 | 'SD': metrics.SD(targets, outputs),
87 | 'CORR': metrics.CORR(targets, outputs),}
88 | ml=np.mean(losses)
89 |
90 | return ml, evaluation
91 |
92 | def main():
93 | F=open(r'../test_set/train_valte_comp.pkl','rb')
94 | content=pickle.load(F)
95 | vina_list= []
96 | graphs = dgl.load_graphs('../test_set/all_in_one_graph_train13851.bin')[0]
97 | labels = pd.read_csv('../test_set/labels_train13851.csv')
98 | vina_terms=open(r'../test_set/Vina_terms13851.pkl','rb')
99 | vina=pickle.load(vina_terms)
100 | for i in range(13851):
101 | if labels.id[i] in vina.keys():
102 | vina_list.append(vina[labels.id[i]])
103 |
104 | device = torch.device("cuda" if torch.cuda.is_available() else "cpu")
105 | compound_train = content[0]
106 | compound_valid = content[1]
107 | compound_test = content[2]
108 |
109 | train_dataset_compound = SepDataset([graphs[i] for i in compound_train], [vina_list[i] for i in compound_train], [labels.id[i] for i in compound_train], [labels.affinity[i] for i in compound_train], ['a_conn','r_conn', 'int_l'])
110 | valid_dataset_compound = SepDataset([graphs[i] for i in compound_valid], [vina_list[i] for i in compound_valid], [labels.id[i] for i in compound_valid], [labels.affinity[i] for i in compound_valid], ['a_conn','r_conn', 'int_l'])
111 | test_dataset_compound = SepDataset([graphs[i] for i in compound_test], [vina_list[i] for i in compound_test], [labels.id[i] for i in compound_test], [labels.affinity[i] for i in compound_test], ['a_conn','r_conn', 'int_l'])
112 |
113 | train_loader_compound = DataLoader(train_dataset_compound, batch_size=8, shuffle=True, num_workers=0, collate_fn=collate_fn,pin_memory=False,drop_last=False,)
114 | valid_loader_compound = DataLoader(valid_dataset_compound, batch_size=8, shuffle=False, num_workers=0, collate_fn=collate_fn)
115 | test_loader_compound = DataLoader(test_dataset_compound, batch_size=8, shuffle=False, num_workers=0, collate_fn=collate_fn)
116 |
117 | model = ModelNew()
118 | model = model.to(device)
119 | optimizer = torch.optim.AdamW(model.parameters(), 1.2e-4, weight_decay=1e-6) ### (model.parameters(), 1e-3, weight_decay=1e-5)
120 | scheduler = torch.optim.lr_scheduler.CosineAnnealingLR(optimizer,T_max=40, eta_min=1e-6)
121 | criterion = torch.nn.MSELoss()
122 |
123 | n_epoch = 80
124 | best_R = 0.0
125 | for epoch in range(n_epoch):
126 | ll = train(model, train_loader_compound, criterion, optimizer,epoch,device)
127 | if epoch%1==0:
128 | l,evaluation = valid(model, valid_loader_compound, criterion,device)
129 | l_, evaluation_ = valid(model, test_loader_compound, criterion,device)
130 | print(f'epoch {epoch+1} train_loss {ll:.5f} valid_loss {l:.5f}')
131 | clear_output()
132 | if evaluation_['CORR']>best_R:
133 | best_R= evaluation_['CORR']
134 | torch.save({'model': model.state_dict()}, '../model/model.pth')
135 | scheduler.step()
136 |
137 | if __name__ == "__main__":
138 | main()
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/test_set/Vina_terms2013.pkl:
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/test_set/Vina_terms2016.pkl:
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/test_set/labels_test2013.csv:
--------------------------------------------------------------------------------
1 | id,affinity
2 | 2v7a,8.30
3 | 1kel,7.28
4 | 3l7b,2.40
5 | 1lol,6.39
6 | 2xys,7.42
7 | 3dd0,9.00
8 | 3d4z,4.89
9 | 1n2v,4.08
10 | 3b3w,4.19
11 | 2x00,11.33
12 | 1u33,4.60
13 | 4tmn,10.17
14 | 1xd0,7.12
15 | 3acw,4.76
16 | 1uto,2.27
17 | 3vh9,6.24
18 | 2wbg,4.45
19 | 3n86,5.64
20 | 3f17,8.63
21 | 1bcu,3.28
22 | 2qft,5.26
23 | 1w4o,5.22
24 | 2zx6,10.60
25 | 3cft,4.19
26 | 3ueu,5.24
27 | 1f8b,5.40
28 | 3n7a,3.70
29 | 2xb8,7.59
30 | 3dxg,2.40
31 | 2x97,5.66
32 | 1qi0,2.35
33 | 2obf,8.85
34 | 3fcq,2.77
35 | 2wca,5.60
36 | 1o3f,7.96
37 | 10gs,6.40
38 | 3ao4,2.07
39 | 2ole,7.25
40 | 3kgp,2.57
41 | 3cj2,4.85
42 | 2zxd,5.22
43 | 3u9q,4.38
44 | 2g70,7.77
45 | 1os0,6.03
46 | 3mss,4.66
47 | 1q8t,4.76
48 | 3coy,6.02
49 | 3gy4,5.10
50 | 2pq9,8.11
51 | 1z95,7.12
52 | 2brb,4.86
53 | 3pxf,4.43
54 | 2vl4,6.01
55 | 1sln,6.64
56 | 1f8d,3.40
57 | 2vot,7.14
58 | 1gpk,5.37
59 | 1o5b,5.77
60 | 4djr,11.52
61 | 2wtv,8.74
62 | 3utu,10.92
63 | 3muz,3.46
64 | 3uex,6.92
65 | 2d3u,6.92
66 | 2xnb,6.83
67 | 3g0w,9.52
68 | 3su5,5.58
69 | 2vw5,8.52
70 | 3g2n,4.09
71 | 3b3s,2.55
72 | 3su2,7.35
73 | 2j78,6.42
74 | 2xbv,8.43
75 | 3imc,2.96
76 | 2yki,9.46
77 | 2p4y,9.00
78 | 2xy9,9.19
79 | 4de1,5.96
80 | 3lka,2.82
81 | 4dew,7.00
82 | 3pww,7.32
83 | 2xdl,3.10
84 | 2hb1,3.80
85 | 3ge7,8.70
86 | 2vo5,4.89
87 | 3ehy,5.85
88 | 3kv2,7.32
89 | 1yc1,6.17
90 | 2weg,6.50
91 | 3jvs,6.54
92 | 3fv1,9.30
93 | 3ozt,4.13
94 | 2cet,8.02
95 | 1q8u,5.96
96 | 3ivg,4.30
97 | 1p1q,4.89
98 | 3l3n,8.18
99 | 1h23,8.35
100 | 2zcq,8.82
101 | 2yfe,6.63
102 | 2d1o,7.70
103 | 2qmj,4.21
104 | 3l4u,7.52
105 | 1lor,11.06
106 | 1hfs,8.70
107 | 2jdu,6.72
108 | 3vd4,4.82
109 | 3nox,8.66
110 | 3e93,8.85
111 | 3myg,10.70
112 | 4des,5.85
113 | 3f3c,6.02
114 | 1hnn,6.24
115 | 1n1m,5.70
116 | 2jdy,4.37
117 | 3mfv,2.52
118 | 4g8m,7.89
119 | 3f3e,7.70
120 | 2yge,5.06
121 | 1sqa,9.21
122 | 3su3,9.13
123 | 2j62,11.34
124 | 3pe2,9.76
125 | 2jdm,5.40
126 | 2qbr,6.33
127 | 2cbj,8.27
128 | 1mq6,11.15
129 | 1f8c,7.40
130 | 3kwa,4.08
131 | 1e66,9.89
132 | 3f3a,4.19
133 | 3nq3,3.78
134 | 2pcp,8.70
135 | 2ymd,3.16
136 | 2zwz,7.79
137 | 1u1b,7.80
138 | 2zjw,7.70
139 | 3uo4,6.52
140 | 2qbp,8.40
141 | 3oe5,6.88
142 | 2x0y,4.60
143 | 2y5h,5.79
144 | 3gcs,7.25
145 | 2vvn,7.30
146 | 1ps3,2.28
147 | 2iwx,6.68
148 | 2gss,4.94
149 | 1r5y,6.46
150 | 3udh,2.85
151 | 3zso,5.12
152 | 3cyx,8.00
153 | 4djv,6.72
154 | 3ejr,8.57
155 | 3i3b,2.23
156 | 1oyt,7.24
157 | 3gnw,9.10
158 | 3bkk,6.08
159 | 2xhm,6.80
160 | 1vso,4.72
161 | 1lbk,3.18
162 | 3zsx,3.28
163 | 1nvq,8.25
164 | 3l4w,6.00
165 | 4de2,4.12
166 | 4gid,10.77
167 | 2fvd,8.52
168 | 3k5v,6.30
169 | 3ebp,5.91
170 | 3gbb,6.90
171 | 3fk1,2.62
172 | 3ag9,8.05
173 | 2w66,4.05
174 | 3f80,4.22
175 | 4gqq,2.89
176 | 2x8z,7.96
177 | 3huc,5.99
178 | 3g2z,2.36
179 | 3bfu,6.27
180 | 3owj,6.07
181 | 3nw9,9.00
182 | 3b68,8.40
183 | 2v00,3.66
184 |
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/test_set/labels_test2016.csv:
--------------------------------------------------------------------------------
1 | id,affinity
2 | 2v7a,8.30
3 | 4dld,5.82
4 | 3l7b,2.40
5 | 3zdg,7.10
6 | 2xys,7.42
7 | 3b65,9.27
8 | 3dd0,9.00
9 | 3d4z,4.89
10 | 1owh,7.40
11 | 2x00,11.33
12 | 4tmn,10.17
13 | 3b5r,8.77
14 | 1z6e,9.72
15 | 3acw,4.76
16 | 3rsx,4.41
17 | 1uto,2.27
18 | 3fur,8.00
19 | 4u4s,2.92
20 | 2wbg,4.45
21 | 3n86,5.64
22 | 1bcu,3.28
23 | 1w4o,5.22
24 | 4ciw,4.82
25 | 4wiv,6.26
26 | 3coz,5.57
27 | 3ueu,5.24
28 | 3n7a,3.70
29 | 3ryj,7.80
30 | 2xb8,7.59
31 | 3dxg,2.40
32 | 2wvt,6.12
33 | 3gr2,2.52
34 | 2c3i,7.60
35 | 4ih5,4.11
36 | 3fcq,2.77
37 | 4j28,5.70
38 | 2wca,5.60
39 | 1o3f,7.96
40 | 3ao4,2.07
41 | 3kgp,2.57
42 | 3gv9,2.12
43 | 4ddk,2.29
44 | 2xii,7.20
45 | 4f09,6.70
46 | 1nc3,5.00
47 | 2xj7,6.66
48 | 1s38,5.15
49 | 3u9q,4.38
50 | 4m0z,5.19
51 | 3aru,3.22
52 | 3u8n,10.17
53 | 1syi,5.44
54 | 5tmn,8.04
55 | 4bkt,3.62
56 | 3arv,5.64
57 | 4f9w,6.94
58 | 1k1i,6.58
59 | 1g2k,7.96
60 | 3mss,4.66
61 | 1q8t,4.76
62 | 2qbq,7.44
63 | 3coy,6.02
64 | 4mgd,4.69
65 | 3gy4,5.10
66 | 3up2,7.40
67 | 1z95,7.12
68 | 2brb,4.86
69 | 4jxs,4.74
70 | 3pxf,4.43
71 | 2wn9,8.52
72 | 4k18,8.96
73 | 3tsk,7.17
74 | 3u8k,8.66
75 | 3u5j,5.61
76 | 4rfm,10.05
77 | 4eky,3.52
78 | 4f2w,11.30
79 | 1gpk,5.37
80 | 4w9c,4.65
81 | 4w9l,5.02
82 | 1ydt,7.32
83 | 3twp,3.92
84 | 1o5b,5.77
85 | 1h22,9.10
86 | 3g31,2.89
87 | 2wtv,8.74
88 | 2j7h,7.19
89 | 3utu,10.92
90 | 4cig,3.67
91 | 3bgz,6.26
92 | 3e5a,8.23
93 | 3uex,6.92
94 | 1z9g,5.64
95 | 3n76,6.85
96 | 4gr0,9.55
97 | 4m0y,6.46
98 | 4ea2,6.44
99 | 4gfm,7.22
100 | 2xnb,6.83
101 | 3g0w,9.52
102 | 2vw5,8.52
103 | 3g2n,4.09
104 | 2j78,6.42
105 | 2xbv,8.43
106 | 4kzq,6.10
107 | 3dx1,3.58
108 | 2wnc,6.32
109 | 3d6q,3.76
110 | 1qf1,7.32
111 | 2yki,9.46
112 | 3f3d,7.16
113 | 2p4y,9.00
114 | 5c28,5.66
115 | 3wtj,6.53
116 | 4de1,5.96
117 | 2wer,7.05
118 | 3lka,2.82
119 | 4cr9,4.10
120 | 4e6q,8.36
121 | 3pww,7.32
122 | 4mme,6.50
123 | 2xdl,3.10
124 | 4agq,5.01
125 | 2hb1,3.80
126 | 4k77,6.63
127 | 2br1,5.14
128 | 4dli,5.62
129 | 3ge7,8.70
130 | 3ehy,5.85
131 | 3uew,6.31
132 | 2zda,8.40
133 | 1yc1,6.17
134 | 3pyy,6.86
135 | 2weg,6.50
136 | 3jvs,6.54
137 | 3fv1,9.30
138 | 4ogj,6.79
139 | 3ary,6.00
140 | 3ozt,4.13
141 | 4w9i,5.96
142 | 2cet,8.02
143 | 3p5o,7.26
144 | 1q8u,5.96
145 | 3jvr,5.72
146 | 1qkt,9.04
147 | 3ivg,4.30
148 | 1p1q,4.89
149 | 4kzu,6.50
150 | 3b27,5.16
151 | 4ivb,8.72
152 | 1h23,8.35
153 | 2zcq,8.82
154 | 2yfe,6.63
155 | 4ddh,3.30
156 | 4abg,3.57
157 | 1ydr,5.52
158 | 3qgy,7.80
159 | 3dx2,6.82
160 | 3cj4,6.51
161 | 3nq9,4.03
162 | 1gpn,6.48
163 | 1pxn,7.15
164 | 4f3c,11.82
165 | 4cra,7.22
166 | 3e93,8.85
167 | 3myg,10.70
168 | 3f3c,6.02
169 | 4ih7,5.24
170 | 1c5z,4.01
171 | 4kz6,3.10
172 | 3ozs,5.33
173 | 3oe4,7.47
174 | 4qd6,8.64
175 | 3e92,8.00
176 | 3f3e,7.70
177 | 2yge,5.06
178 | 1sqa,9.21
179 | 3syr,5.10
180 | 3ui7,9.00
181 | 4jia,9.22
182 | 4eor,6.30
183 | 2qbr,6.33
184 | 4j3l,7.80
185 | 1mq6,11.15
186 | 5dwr,11.22
187 | 3qqs,5.82
188 | 4crc,8.72
189 | 3kwa,4.08
190 | 1e66,9.89
191 | 3f3a,4.19
192 | 5c2h,11.09
193 | 3uuo,7.96
194 | 3gc5,7.26
195 | 1p1n,6.80
196 | 2ymd,3.16
197 | 2cbv,5.48
198 | 3b1m,8.48
199 | 4jfs,5.27
200 | 3jya,6.89
201 | 3rlr,7.52
202 | 1u1b,7.80
203 | 3prs,7.82
204 | 2p15,10.30
205 | 3uo4,6.52
206 | 5aba,2.98
207 | 4lzs,4.80
208 | 2qbp,8.40
209 | 3oe5,6.88
210 | 1o0h,5.92
211 | 2y5h,5.79
212 | 2r9w,5.10
213 | 2pog,9.54
214 | 2vvn,7.30
215 | 4e5w,7.66
216 | 3arp,7.15
217 | 4ivc,10.00
218 | 1ps3,2.28
219 | 5a7b,3.57
220 | 2iwx,6.68
221 | 1r5y,6.46
222 | 3udh,2.85
223 | 1nc1,6.12
224 | 4de3,5.52
225 | 3zso,5.12
226 | 4ivd,9.52
227 | 4djv,6.72
228 | 3ejr,8.57
229 | 4agp,4.69
230 | 4w9h,6.73
231 | 3o9i,11.82
232 | 1eby,9.70
233 | 2qnq,6.11
234 | 1oyt,7.24
235 | 3gnw,9.10
236 | 4j21,7.41
237 | 1vso,4.72
238 | 4pcs,7.85
239 | 3zsx,3.28
240 | 4jsz,2.30
241 | 1nvq,8.25
242 | 1bzc,4.92
243 | 4de2,4.12
244 | 4gid,10.77
245 | 3uev,5.89
246 | 2fvd,8.52
247 | 4gkm,5.17
248 | 3k5v,6.30
249 | 3ebp,5.91
250 | 3gbb,6.90
251 | 2w66,4.05
252 | 2fxs,6.06
253 | 3r88,4.82
254 | 3rr4,4.55
255 | 2vkm,8.74
256 | 4agn,3.97
257 | 3kr8,8.10
258 | 4qac,9.40
259 | 4owm,2.96
260 | 3arq,6.40
261 | 2zb1,6.32
262 | 3g2z,2.36
263 | 4hge,7.92
264 | 4twp,10.00
265 | 2w4x,4.85
266 | 3wz8,5.82
267 | 3fv2,8.11
268 | 1lpg,7.09
269 | 3nw9,9.00
270 | 4llx,2.89
271 | 4eo8,8.15
272 | 3nx7,8.10
273 | 1y6r,10.11
274 | 4ty7,9.52
275 | 3b68,8.40
276 | 2al5,8.40
277 | 2qe4,7.96
278 | 4x6p,8.30
279 | 2v00,3.66
280 | 3zt2,2.84
281 |
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