Supplementary Material Automatic parametrization of non-polar implicit solvent models for the blind prediction of solvation free energies Bao Wang1, Zhixiong Zhao1, and Guo-Wei Wei1;2;3 ∗ 1Department of Mathematics Michigan State University, MI 48824, USA 2Department of Electrical and Computer Engineering Michigan State University, MI 48824, USA 3Department of Biochemistry and Molecular Biology Michigan State University, MI 48824, USA August 12, 2016 The SAMPL0 molecular information and the predicted solvation free energy with different charge method and atomic radius force field parametrization are listed in Table1-4. The SAMPL1-SAMPL4 results are listed in Tables5-20, respec- tively. For the Sampl0-Sampl2 test sets, the RMS errors that inside and outside the parenthesis denote that when the molecules contain Br atom are included and excluded, respectively. The mean average error (MAE) for different force field parametrization are also included. The information of 668 molecules is given in Table 21. exp pred Table S1: The experimental and predicted solvation free energy for the SAMPL0 test set. ∆G is the experimental solvation free energy, ∆GAM1−BCC, pred pred pred ∆GMulliken, ∆GGasteiger, and ∆GSIESTA are the predicted solvation free energy with four different types of charges. The Amber6 force field are employed for the atomic radius parametrization. The energy data are all in the unit of kcal/mol. exp pred pred pred pred Solute Name ∆G ∆GAM1−BCC ∆GMulliken ∆GGasteiger ∆GSIESTA 1,1-diethoxyethane -3.28 -3.30 -1.32 -3.30 -0.28 dimethoxymethane -2.93 -3.66 -1.91 -3.40 -1.96 1-acetoxyethyl acetate -4.97 -6.63 -6.40 -5.79 -5.51 diethyl propanedioate -6.00 -8.27 -6.58 -6.17 -7.14 2-acetoxyethyl acetate -6.34 -7.95 -7.16 -6.72 -6.93 2,3-diacetoxypropyl acetate -8.84 -11.70 -10.34 -9.41 -9.89 1,2-diethoxyethane -3.54 -3.34 -3.77 -3.30 -3.61 1,4-dioxane -5.06 -5.10 -4.58 -4.62 -4.98 benzyl chloride -1.93 -2.90 -2.38 -1.77 -1.79 N,N-4-trimethylbenzamide -9.76 -9.50 -12.32 -13.04 -10.44 ethylsulfanylethane -1.46 -1.56 -1.16 -1.37 -1.59 1-chloro-2-(2-chloroethoxy)ethane -4.23 -6.13 -4.52 -4.76 -4.02 4-methoxy-N,N-dimethyl-benzamide -11.01 -11.28 -10.73 -10.74 -9.95 phenyl formate -3.82 -5.46 -5.34 -5.29 -4.13 m-bis(trifluoromethyl)benzene 1.07 1.45 1.04 2.01 1.29 imidazole -9.63 -9.01 -7.18 -6.71 -8.61 benzyl bromide -2.38 -2.78 -1.55 -2.05 NA RMSE 1.30 (1.26) 1.27 (1.25) 1.23 (1.20) 0.99 (NA) ME 0.78 (0.76) -0.18 (-0.12) -0.16 (-0.13) 0.13 (NA) ∗Address correspondences to Guo-Wei Wei. E-mail: [email protected] 1 2 exp pred Table S2: The experimental and predicted solvation free energy for the SAMPL 0 test set. ∆G is the experimental solvation free energy, ∆GAM1−BCC, pred pred pred ∆GMulliken, ∆GGasteiger, and ∆GSIESTA are the predicted solvation free energy with four different types of charges. The Amber bondi force field are employed for the atomic radius parametrization. The energy data are all in the unit of kcal/mol. exp pred pred pred pred Solute Name ∆G ∆GAM1−BCC ∆GMulliken ∆GGasteiger ∆GSIESTA 1,1-diethoxyethane -3.28 -3.58 -1.50 -3.75 -1.13 dimethoxymethane -2.93 -3.90 -2.08 -3.77 -2.59 1-acetoxyethyl acetate -4.97 -6.63 -6.46 -5.80 -5.41 diethyl propanedioate -6.00 -8.34 -6.63 -6.21 -7.83 2-acetoxyethyl acetate -6.34 -8.03 -7.28 -6.75 -7.23 2,3-diacetoxypropyl acetate -8.84 -11.99 -10.56 -9.43 -8.67 1,2-diethoxyethane -3.54 -3.29 -3.64 -3.41 -4.09 1,4-dioxane -5.06 -5.24 -4.75 -4.73 -5.44 benzyl chloride -1.93 -3.02 -2.48 -1.80 -2.17 N,N-4-trimethylbenzamide -9.76 -9.43 -12.38 -13.28 -11.40 ethylsulfanylethane -1.46 -1.54 -0.99 -1.41 -1.70 1-chloro-2-(2-chloroethoxy)ethane -4.23 -6.40 -4.71 -4.95 -4.11 4-methoxy-N,N-dimethyl-benzamide -11.01 -11.34 -10.84 -10.90 -10.75 phenyl formate -3.82 -5.55 -5.41 -5.29 -3.69 m-bis(trifluoromethyl)benzene 1.07 1.36 0.92 2.07 1.06 imidazole -9.63 -9.01 -7.09 -6.64 -8.49 benzyl bromide -2.38 -2.85 -1.55 -2.09 NA RMSE 1.40 (1.37) 1.30 (1.27) 1.30 (1.27) 0.93 (NA) ME 0.88 (0.86) -0.26 (-0.20) -0.27 (-0.24) -0.12 (NA) 3 exp pred Table S3: The experimental and predicted solvation free energy for the SAMPL 0 test set. ∆G is the experimental solvation free energy, ∆GAM1−BCC, pred pred pred ∆GMulliken, ∆GGasteiger, and ∆GSIESTA are the predicted solvation free energy with four different types of charges. The Amber mbondi2 force field are employed for the atomic radius parametrization. The energy data are all in the unit of kcal/mol. exp pred pred pred pred Solute Name ∆G ∆GAM1−BCC ∆GMulliken ∆GGasteiger ∆GSIESTA 1,1-diethoxyethane -3.28 -3.58 -1.50 -3.75 -1.13 dimethoxymethane -2.93 -3.90 -2.08 -3.77 -2.59 1-acetoxyethyl acetate -4.97 -6.63 -6.46 -5.80 -5.41 diethyl propanedioate -6.00 -8.34 -6.63 -6.21 -7.83 2-acetoxyethyl acetate -6.34 -8.03 -7.28 -6.75 -7.23 2,3-diacetoxypropyl acetate -8.84 -11.99 -10.56 -9.43 -8.67 1,2-diethoxyethane -3.54 -3.29 -3.64 -3.41 -4.09 1,4-dioxane -5.06 -5.24 -4.75 -4.73 -5.44 benzyl chloride -1.93 -3.02 -2.48 -1.80 -2.14 N,N-4-trimethylbenzamide -9.76 -9.78 -12.60 -13.41 -12.31 ethylsulfanylethane -1.46 -1.54 -0.99 -1.41 -1.70 1-chloro-2-(2-chloroethoxy)ethane -4.23 -6.40 -4.71 -4.95 -4.12 4-methoxy-N,N-dimethyl-benzamide -11.01 -11.55 -10.97 -10.97 -11.28 phenyl formate -3.82 -5.55 -5.41 -5.29 -3.69 m-bis(trifluoromethyl)benzene 1.07 1.36 0.92 2.07 1.06 imidazole -9.63 -8.87 -6.98 -6.59 -7.86 benzyl bromide -2.38 -2.85 -1.55 -2.09 NA RMSE 1.41 (1.37) 1.34 (1.32) 1.33 (1.29) 1.10 (NA) ME 0.91 (0.88) 0.27 (0.21) -0.28 (-0.25) -0.17 (NA) exp pred Table S4: The experimental and predicted solvation free energy for the SAMPL 0 test set. ∆G is the experimental solvation free energy, ∆GAM1−BCC, pred pred pred ∆GMulliken, ∆GGasteiger, and ∆GSIESTA are the predicted solvation free energy with four different types of charges. The ZAP9 force field are employed for the atomic radius parametrization. The energy data are all in the unit of kcal/mol. exp pred pred pred pred Solute Name ∆G ∆GAM1−BCC ∆GMulliken ∆GGasteiger ∆GSIESTA 1,1-diethoxyethane -3.28 -2.27 -0.72 -2.58 -0.82 dimethoxymethane -2.93 -2.44 -1.25 -2.40 -2.21 1-acetoxyethyl acetate -4.97 -6.26 -6.39 -5.66 -5.38 diethyl propanedioate -6.00 -7.87 -6.63 -5.97 -8.06 2-acetoxyethyl acetate -6.34 -7.47 -7.09 -6.43 -7.07 2,3-diacetoxypropyl acetate -8.84 -11.03 -10.34 -9.07 -9.53 1,2-diethoxyethane -3.54 -3.19 -3.52 -3.39 -4.07 1,4-dioxane -5.06 -5.00 -4.77 -4.49 -5.69 benzyl chloride -1.93 -2.67 -2.23 -1.74 -3.15 N,N-4-trimethylbenzamide -9.76 -9.94 -12.14 -13.14 -10.30 ethylsulfanylethane -1.46 -1.41 -1.05 -1.41 -1.85 1-chloro-2-(2-chloroethoxy)ethane -4.23 -6.08 -4.60 -4.58 -4.97 4-methoxy-N,N-dimethyl-benzamide -11.01 -11.00 -10.66 -10.78 -9.95 phenyl formate -3.82 -5.65 -5.51 -5.21 -3.93 m-bis(trifluoromethyl)benzene 1.07 3.86 2.42 3.73 2.35 imidazole -9.63 -10.39 -7.24 -6.83 -10.57 benzyl bromide -2.38 -2.85 -1.55 -2.09 NA RMSE 1.33 (1.29) 1.39 (1.37) 1.37 (1.33) 1.08 (NA) ME 0.44 (0.44) 0.00 (0.05) 0.11 (0.12) -0.21 (NA) exp pred Table S5: The experimental and predicted solvation free energy for the SAMPL 1 test set. ∆G is the experimental solvation free energy, ∆GAM1−BCC, pred pred pred ∆GMulliken, ∆GGasteiger, and ∆GSIESTA are the predicted solvation free energy with four different types of charges. The Amber6 force field are employed for the atomic radius parametrization. The energy data are all in the unit of kcal/mol. exp pred pred pred pred Solute Name ∆G ∆GAM1−BCC ∆GMulliken ∆GGasteiger ∆GSIESTA lindane -5.44 -6.72 -4.65 -2.88 -4.40 isobutyl nitrate -1.88 -1.87 -1.80 -1.85 -1.77 butyl nitrate -2.09 -1.95 -1.87 -1.90 -1.42 [(2S)-butan-2-yl] nitrate -1.82 -2.19 -1.97 -1.78 -0.98 1,2-dinitroxyethane -5.73 -3.45 -4.30 -4.01 -4.31 1,2-dinitroxypropane -4.95 -5.58 -4.69 -4.63 -5.02 4 Table 5 – continued from previous page exp pred pred pred pred Solute Name ∆G ∆GAM1−BCC ∆GMulliken ∆GGasteiger ∆GSIESTA ethion -6.10 -6.87 -12.72 -11.38 -12.20 captan -9.01 -7.60 -6.99 -4.56 -7.13 trichloro(nitro)methane -1.45 -0.90 -2.32 -1.93 -3.89 heptachlor -2.55 -4.78 -4.46 -2.44 -5.05 chlordane -3.44 -6.83 -5.88 -2.61 -4.03 dichlobenil -4.71 -3.63 -2.33 -3.72 -5.51 fenuron -9.13 -9.78 -8.32 -8.26 -8.25 N-(3,4-dichlorophenyl)propanimidic acid -7.78 -8.22 -6.24 -7.10 -10.35 alachlor -8.21 -7.57 -7.14 -3.25 -5.86 pebulate -3.64 -4.93 -4.51 -0.93 -5.69 N,N-dipropyl(propylsulfanyl)formamide -4.13 -4.80 -4.22 -0.59 -5.57 dicamba -9.86 -13.10 -7.08 -7.89 -13.94 bensulfuron -17.17 -24.05 -32.80 -30.70 -22.30 3,5,5-trimethylcyclohex-2-en-1-one -5.18 -3.99 -2.61 -2.68 -4.29 1,4,5,8-tetramino-anthraquinone -8.94 -14.62 -10.12 -12.97 -10.82 5-Amino-4-chloro-2-phenylpyridazin-3(2H)-one -16.43 -10.35 -16.16 -16.72 -8.92 1-amino-4-anilino-anthraquinone -7.44 -9.90 -7.81 -11.46 -8.94 4-amino-4’-nitroazobenzene -11.24 -7.95 -9.95 -10.19 -10.73 1-N,1-N-diethyl-2,6-dinitro-4-(trifluoromethyl)benzene-1,3-diamine -5.66 -3.83 -5.10 -10.12 -7.03 terbacil -11.14 -11.48 -6.52 -5.91 -8.68 simazine -10.22 -10.29 -10.24 -5.79 -8.95 aldicarb -9.84 -9.49 -6.79 -6.18 -9.39 carbofuran -9.61 -9.95 -9.22 -7.13 -8.24 trifluralin -3.25 -1.17 -2.69 -9.49 -5.00 nitralin -7.98 -11.34 -17.79 -16.11 -9.29 dinoseb -6.23 -9.67 -7.61 -9.87 -12.93 nitroxyacetone -5.99 -9.84 -8.43 -8.39 -8.14 2-(nitrooxy)ethan-1-ol -8.18 -3.31 -9.26 -7.72 -2.85 N-butyl-N-ethyl-2,6-dinitro-4-(trifluoromethyl)aniline -3.51 -1.34 -2.77 -9.51 -7.93 profluralin -2.45 -0.55 -2.29 -9.60 -5.27 pirimor -9.41 -11.73 -11.70 -8.92 -7.60 4-dimethylamino-azobenzene -6.66 -5.52 -9.75 -10.59 -7.32 endrin -4.82 -7.79 -6.20 -5.24 -4.90 endrin -4.82 -8.03 -7.05 -5.17 -3.73 trichlorfon -12.74 -14.89 -21.45 -3.32 -11.91