Supplementary material
Equations for calculating the octanol/water distribution coefficients:
(Eq. S1)
(Eq.S2)
(Eq.S3)
(Eq.S4)
S1
Table S1.Comparison of templates and homology models
Receptors / TempleProtein e / Sequence for homology model f / Sequence identity / Sequencesimilarity / Homology model
RMSDa(Å) / Homology model
Score b
Ala-racemase / 2rjG
(2.40 Å) / Q5E849 / 58.9% / 77.9% / 0.87 / 0.97
Pen-1B / 3FWM
(2.16 Å) / B5FAP4 / 40.6% / 60.6% / 1.16 / 0.94
Pen-3A / 3OCL
(2.30 Å) / B5E2P4 / 39.3% / 58.4% / 0.94 / 0.90
Dhps / 1AJ0
(2.0 Å) / Q5E7M1 / 60.1% / 80.2% / 0.88 / 0.96
Dhfr / 3FRB
(2.0 Å) / Q5E867 / 39.6% / 62.9% / 1.12 / 0.99
30S c / 1HNW
(3.40 Å) / - / - / - / - / -
50S d / 3OFC
(3.19 Å) / - / - / - / - / -
DNAgyrase / 2YP3
(2.62 Å) / B5FDT9 / 77.8% / 89.5% / 0.87 / 0.97
RNApolymerase / 2A69
(2.50 Å) / B5FC88 / 41.0% / 58.4% / 0.96 / 0.92
a RMSD values are calculated by using a alignment protocol in Discovery studio 2.5.5;
b The ratio of verify-scores to verify expected high score are obtained by using a verify protein protocol;
c, d The homology models of ribosome subunit were not performed because of the complexity in structure;
e The sequences of V.fischeri were obtained in Uni-prot (
f The models were obtained in RCSB protein data bank (
Table S2. Observed and predicted chronic toxicity data of different binary mixtures
Mixture(A: TMP) / A:TMP / / / / / / ( molL-1)
Observed / Predicted / Residuals
1# : 9# / 1:1b / 9.46E-3 / 9.91E-1 / -4.90 / -2.84E-2 / 7.26E-1 / 5.29 / 5.69 / -0.40
2# : 9# / 1:1b / 1.04E-2 / 9.90E-1 / -5.56 / -3.11E-2 / 7.25E-1 / 5.46 / 5.67 / -0.21
3# : 9# a / 1:1b / 2.14E-2 / 9.79E-1 / -2.22 / -6.47E-2 / 7.21E-1 / 5.50 / 5.76 / -0.26
4# : 9# / 1:1b / 1.01E-2 / 9.90E-1 / -2.65 / -3.04E-2 / 7.26E-1 / 5.51 / 5.74 / -0.23
5# : 9# / 1:1b / 4.77E-2 / 9.52E-1 / -8.57 / -1.46E-1 / 7.09E-1 / 5.60 / 5.60 / 0.00
6# : 9# / 1:1b / 8.93E-1 / 1.07E-1 / -3.35E-1 / -6.67 / 1.41E-2 / 5.50 / 6.00 / -0.50
7# : 9# / 1:1b / 9.22E-1 / 7.84E-2 / -2.19E-1 / -7.61 / 8.60E-1 / 5.17 / 5.13 / 0.04
8# : 9# / 1:1b / 7.96E-1 / 2.04E-1 / -6.47E-1 / -4.74 / 4.11E-1 / 5.73 / 5.75 / -0.02
2# : 9# / 104:1 / 1.00 / 1.60E-4 / -1.95E-4 / -2.61E+1 / -2.95 / 7.35 / 7.41 / -0.06
2# : 9# / 103.5:1 / 1.00 / 5.00E-4 / -6.08E-4 / -2.27E+1 / -2.53 / 7.21 / 7.25 / -0.04
2# : 9# / 103:1 / 9.98E-1 / 1.59E-3 / -1.94E-3 / -1.93E+1 / -2.06 / 7.13 / 7.05 / 0.08
2# : 9# / 102.5:1 / 9.95E-1 / 4.95E-3 / -6.03E-3 / -1.59E+1 / -1.57 / 7.02 / 6.84 / 0.18
2# : 9# a / 102:1 / 9.84E-1 / 1.57E-2 / -1.92E-2 / -1.24E+1 / -1.07 / 6.94 / 6.62 / 0.32
2# : 9# / 101.5:1 / 9.53E-1 / 4.74E-2 / -5.91E-2 / -9.11 / -5.94E-1 / 6.77 / 6.40 / 0.37
2# : 9# / 10:1 / 8.63E-1 / 1.37E-1 / -1.80E-1 / -5.93 / -1.32E-1 / 6.67 / 6.19 / 0.48
2# : 9# / 100.5:1 / 6.68E-1 / 3.32E-1 / -4.91E-1 / -3.29 / 2.52E-1 / 6.74 / 6.01 / 0.73
2# : 9# / 1:1 / 3.86E-1 / 6.14E-1 / -1.16 / -1.46 / 5.18E-1 / 6.65 / 5.87 / 0.77
2# : 9# a / 1:100.5 / 1.64E-1 / 8.36E-1 / -2.20 / -5.35E-1 / 6.52E-1 / 6.19 / 5.79 / 0.40
2# : 9# / 1:10 / 5.91E-2 / 9.41E-1 / -3.44 / -1.82E-1 / 7.04E-1 / 5.69 / 5.73 / -0.04
2# : 9# / 1:101.5 / 1.92E-2 / 9.81E-1 / -4.80 / -5.80E-2 / 7.22E-1 / 5.35 / 5.69 / -0.34
2# : 9# / 1:102 / 6.24E-3 / 9.94E-1 / -6.17 / -1.87E-2 / 7.27E-1 / 5.27 / 5.65 / -0.39
2# : 9# / 1:102.5 / 1.96E-3 / 9.98E-1 / -7.58 / -5.86E-3 / 7.29E-1 / 5.26 / 5.62 / -0.36
2# : 9# / 1:103 / 6.30E-4 / 9.99E-1 / -8.96 / -1.88E-3 / 7.30E-1 / 5.27 / 5.58 / -0.31
2# : 9# / 1:103.5 / 2.00E-4 / 1.00 / -1.04E+1 / -5.98E-4 / 7.30E-1 / 5.23 / 5.54 / -0.32
2# : 9# / 1:104 / 6.00E-5 / 1.00 / -1.18E+1 / -1.79E-4 / 7.30E-1 / 5.32 / 5.51 / -0.19
5# : 9# a / 104:1 / 1.00 / 1.10E-4 / -3.10E-4 / -2.72E+1 / -2.14 / 6.80 / 6.56 / 0.24
5# : 9# / 103.5:1 / 1.00 / 3.50E-4 / -9.87E-4 / -2.38E+1 / -2.07 / 6.84 / 6.74 / 0.10
5# : 9# / 103:1 / 9.99E-1 / 1.11E-3 / -3.13E-3 / -2.03E+1 / -1.90 / 6.83 / 6.83 / 0.00
5# : 9# / 102.5:1 / 9.97E-1 / 3.47E-3 / -9.80E-3 / -1.69E+1 / -1.60 / 6.82 / 6.79 / 0.03
5# : 9# / 102:1 / 9.89E-1 / 1.10E-2 / -3.12E-2 / -1.35E+1 / -1.18 / 6.78 / 6.64 / 0.14
5# : 9# / 101.5:1 / 9.66E-1 / 3.36E-2 / -9.64E-2 / -1.01E+1 / -7.28E-1 / 6.83 / 6.45 / 0.37
5# : 9# / 10:1 / 9.00E-1 / 1.00E-1 / -2.97E-1 / -6.88 / -2.65E-1 / 6.77 / 6.25 / 0.52
5# : 9# / 100.5:1 / 7.42E-1 / 2.58E-1 / -8.41E-1 / -4.05 / 1.43E-1 / 6.56 / 6.05 / 0.51
5# : 9# / 1:1 / 4.73E-1 / 5.27E-1 / -2.11 / -1.92 / 4.52E-1 / 6.34 / 5.88 / 0.46
5# : 9# a / 1:100.5 / 2.19E-1 / 7.81E-1 / -4.28 / -7.39E-1 / 6.23E-1 / 5.85 / 5.75 / 0.10
5# : 9# a / 1:10 / 8.24E-2 / 9.18E-1 / -7.03 / -2.57E-1 / 6.93E-1 / 5.41 / 5.65 / -0.24
5# : 9# / 1:101.5 / 2.73E-2 / 9.73E-1 / -1.01E+1 / -8.27E-2 / 7.18E-1 / 5.39 / 5.56 / -0.16
5# : 9# / 1:102 / 8.90E-3 / 9.91E-1 / -1.33E+1 / -2.67E-2 / 7.26E-1 / 5.35 / 5.47 / -0.13
5# : 9# / 1:102.5 / 2.80E-3 / 9.97E-1 / -1.66E+1 / -8.38E-3 / 7.29E-1 / 5.37 / 5.39 / -0.02
5# : 9# / 1:103 / 9.00E-4 / 9.99E-1 / -1.98E+1 / -2.69E-3 / 7.30E-1 / 5.45 / 5.30 / 0.14
5# : 9# / 1:103.5 / 2.80E-4 / 1.00 / -2.31E+1 / -8.37E-4 / 7.30E-1 / 5.40 / 5.22 / 0.18
5# : 9# / 1:104 / 9.00E-5 / 1.00 / -2.63E+1 / -2.69E-4 / 7.30E-1 / 5.44 / 5.14 / 0.30
6# : 9# / 104:1 / 1.00 / 9.00E-5 / -2.41E-4 / -2.78E+1 / 8.69E-1 / 4.14 / 3.66 / 0.48
6# : 9# / 103.5:1 / 1.00 / 2.70E-4 / -7.24E-4 / -2.46E+1 / 8.69E-1 / 4.28 / 3.90 / 0.38
6# : 9# a / 103:1 / 9.99E-1 / 8.70E-4 / -2.33E-3 / -2.11E+1 / 8.69E-1 / 4.62 / 4.15 / 0.47
6# : 9# / 102.5:1 / 9.97E-1 / 2.72E-3 / -7.30E-3 / -1.77E+1 / 8.69E-1 / 4.70 / 4.40 / 0.30
6# : 9# / 102:1 / 9.91E-1 / 8.65E-3 / -2.33E-2 / -1.42E+1 / 8.68E-1 / 4.92 / 4.65 / 0.27
6# : 9# / 101.5:1 / 9.73E-1 / 2.65E-2 / -7.21E-2 / -1.08E+1 / 8.66E-1 / 5.14 / 4.89 / 0.25
6# : 9# / 10:1 / 9.20E-1 / 8.03E-2 / -2.24E-1 / -7.54 / 8.59E-1 / 5.38 / 5.13 / 0.25
6# : 9# / 100.5:1 / 7.86E-1 / 2.14E-1 / -6.46E-1 / -4.60 / 8.43E-1 / 5.50 / 5.35 / 0.15
6# : 9# / 1:1 / 5.34E-1 / 4.66E-1 / -1.68 / -2.28 / 8.10E-1 / 5.69 / 5.53 / 0.16
6# : 9# / 1:100.5 / 2.64E-1 / 7.36E-1 / -3.57 / -9.15E-1 / 7.71E-1 / 5.69 / 5.61 / 0.07
6# : 9# / 1:10 / 1.03E-1 / 8.97E-1 / -6.10 / -3.24E-1 / 7.47E-1 / 5.65 / 5.61 / 0.04
6# : 9# / 1:101.5 / 3.46E-2 / 9.65E-1 / -9.02 / -1.05E-1 / 7.36E-1 / 5.55 / 5.57 / -0.02
6# : 9# / 1:102 / 1.13E-2 / 9.89E-1 / -1.20E+1 / -3.40E-2 / 7.32E-1 / 5.48 / 5.50 / -0.01
6# : 9# / 1:102.5 / 3.57E-3 / 9.96E-1 / -1.51E+1 / -1.07E-2 / 7.31E-1 / 5.42 / 5.42 / 0.00
6# : 9# / 1:103 / 1.14E-3 / 9.99E-1 / -1.82E+1 / -3.41E-3 / 7.30E-1 / 5.38 / 5.35 / 0.03
6# : 9# / 1:103.5 / 3.60E-4 / 1.00 / -2.12E+1 / -1.08E-3 / 7.30E-1 / 5.33 / 5.27 / 0.06
6# : 9# / 1:104 / 1.10E-4 / 1.00 / -2.44E+1 / -3.29E-4 / 7.30E-1 / 5.32 / 5.19 / 0.14
7# : 9# / 104:1 / 1.00 / 1.10E-4 / -3.24E-4 / -2.72E+1 / -2.91E-1 / 4.18 / 4.80 / -0.62
7# : 9# / 103.5:1 / 1.00 / 3.30E-4 / -9.73E-4 / -2.40E+1 / -2.90E-1 / 4.43 / 5.04 / -0.61
7# : 9# / 103:1 / 9.99E-1 / 1.07E-3 / -3.16E-3 / -2.04E+1 / -2.87E-1 / 4.60 / 5.29 / -0.70
7# : 9# a / 102.5:1 / 9.97E-1 / 3.33E-3 / -9.84E-3 / -1.70E+1 / -2.77E-1 / 4.82 / 5.53 / -0.71
7# : 9# / 102:1 / 9.89E-1 / 1.06E-2 / -3.14E-2 / -1.36E+1 / -2.49E-1 / 5.12 / 5.75 / -0.63
7# : 9# / 101.5:1 / 9.68E-1 / 3.23E-2 / -9.69E-2 / -1.03E+1 / -1.75E-1 / 5.36 / 5.92 / -0.56
7# : 9# / 10:1 / 9.03E-1 / 9.66E-2 / -2.99E-1 / -6.98 / -8.38E-3 / 5.45 / 5.99 / -0.54
7# : 9# / 100.5:1 / 7.50E-1 / 2.50E-1 / -8.50E-1 / -4.14 / 2.38E-1 / 5.72 / 5.95 / -0.24
7# : 9# / 1:1 / 4.83E-1 / 5.17E-1 / -2.14 / -1.97 / 4.80E-1 / 5.77 / 5.85 / -0.08
7# : 9# / 1:100.5 / 2.26E-1 / 7.74E-1 / -4.38 / -7.66E-1 / 6.31E-1 / 5.60 / 5.74 / -0.13
7# : 9# / 1:10 / 8.56E-2 / 9.14E-1 / -7.25 / -2.67E-1 / 6.95E-1 / 5.47 / 5.64 / -0.17
7# : 9# / 1:101.5 / 2.84E-2 / 9.72E-1 / -1.05E+1 / -8.61E-2 / 7.19E-1 / 5.54 / 5.55 / -0.01
7# : 9# a / 1:102 / 9.27E-3 / 9.91E-1 / -1.38E+1 / -2.78E-2 / 7.26E-1 / 5.50 / 5.46 / 0.04
7# : 9# / 1:102.5 / 2.92E-3 / 9.97E-1 / -1.72E+1 / -8.74E-3 / 7.29E-1 / 5.34 / 5.37 / -0.03
7# : 9# / 1:103 / 9.30E-4 / 9.99E-1 / -2.06E+1 / -2.78E-3 / 7.30E-1 / 5.28 / 5.28 / -0.01
7# : 9# a / 1:103.5 / 2.90E-4 / 1.00 / -2.40E+1 / -8.67E-4 / 7.30E-1 / 5.25 / 5.20 / 0.06
7# : 9# / 1:104 / 9.00E-5 / 1.00 / -2.75E+1 / -2.69E-4 / 7.30E-1 / 5.25 / 5.11 / 0.14
Note: above toxicity data was obtained on the variation of mass concentrations as the following ratio: 1:104, 1:103.5, 1:103, 1:102.5, 1:102, 1:101.5, 1:10, 1:100.5, 1:1, 100.5: 1, 10: 1, 101.5: 1, 102: 1, 102.5: 1, 103: 1, 103.5: 1, 104: 1; a Validation set;b toxicity data obtained at the equitoxic ration.
S1
Figure S1.The Ramachandran plot of developed homology models. (A) Ala-racemase, (B) Pen-1B, (C) Pen-3A, (D) Dhps, (E) Dhfr, (F) DNA-gyrase, (G) RNA-polymerase. (○) the inside residue, (△) the outside amino acid, ( ) overlap, ( ) hard-sphere.
Fig.S2.The interaction of antibiotics with receptors: (A) SMZ -DHPS, (B) SMZ-DHFR, (C)TMP-DHFR and (D) TMP-DHP.
S1
S1