suppmat_1760. 101KB Jun 05 2011 09:30:56 PM
❚❤❡ P❛r❛♠❡t❡r✐③❛t✐♦♥ ❛♥❞ ❱❛❧✐❞❛t✐♦♥ ♦❢ ●❡♥❡r❛❧✐③❡❞ ❇♦r♥ ▼♦❞✲
❡❧s ✉s✐♥❣ t❤❡ P❛✐r✇✐s❡ ❉❡s❝r❡❡♥✐♥❣ ❆♣♣r♦①✐♠❛t✐♦♥
Julien Michel, Jonathan W. Essex
School of Chemistry, University of Southampton, Highfield, Southampton, SO17 1BJ, UK
Richard D. Taylor
Astex Technology Ltd, 436 Cambridge Science Park, Milton Road Cambridge, CB4 0QA, UK
Supplementary Information
1
I : Experimental and Predicted Free energies of hydration for the four
different GBSA models
Energies are in kcal.mol−1 .
Table 1: Dataset - Training I
Compound
Linear Alkanes
ethane
propane
butane
hexane
heptane
octane
Branched Alkanes
2-methylpentane
2,4-dimethylpentane
neopentane
Cycloalkanes
cyclopropane
cyclohexane
methyl-cyclohexane
cis-1,2-dimethylcyclohexane
Alkenes
2-methylpropene
1-butene
cyclopentene
(E)2-pentene
1-pentene
trans-1,3-butadiene
Alkynes
propyne
1-butyne
1-hexyne
Exp
PDAnum-1
PDAnum-2
PDAexp-1
PDAexp-2
1.80
2.00
2.20
2.50
2.60
2.90
1.39
1.60
1.82
2.28
2.51
2.74
1.39
1.60
1.82
2.28
2.28
2.74
1.57
1.79
2.01
2.47
2.71
2.94
1.57
1.78
2.00
2.45
2.68
2.91
2.50
2.90
2.50
2.15
2.37
1.94
2.15
2.37
1.94
2.36
2.49
2.06
2.35
2.47
2.04
0.80
1.20
1.70
1.60
1.12
2.00
2.22
2.36
1.12
2.00
2.22
2.36
1.26
2.06
2.26
2.35
1.24
2.05
2.24
2.33
1.20
1.40
0.60
1.30
1.70
0.60
1.03
1.03
0.88
1.45
1.28
0.03
1.03
1.03
0.88
1.45
1.28
0.03
1.11
1.19
0.80
1.51
1.41
0.21
1.09
1.17
0.79
1.47
1.38
0.19
-0.30
-0.20
0.30
-0.19
0.22
0.77
-0.19
0.22
0.77
0.07
0.46
1.02
0.07
0.46
1.01
1
Table 2: Dataset - Training II
Compound
Arenes
anthracene
benzene
ethylbenzene
o-xylene
m-xylene
toluene
Alcohols
2-butanol
3-pentanol
4-methylphenol
ethanol
1-octanol
phenol
t-butanol
Aldehydes
benzaldehyde
butanal
ethanal
propanal
Ketones
2-butanone
2-hexanone
3,3-dimethylbutanone
3-pentanone
acetone
cyclopentanone
Carboxylic Acids
acetic acid
propanoic acid
butanoic acid
pentanoic acid
Esters
butylacetate
ethylacetate
methylacetate
methylbenzoate
methylpentanoate
propylacetate
Ethers
1,2-dimethoxyethane
1,4-dioxane
anisole
diethylether
methylisopropylether
Tetrahydrofuran
Exp
PDAnum-1
PDAnum-2
PDAexp-1
PDAexp-2
-4.20
-0.90
-0.80
-0.90
-0.80
-0.90
-3.04
-1.30
-0.46
-0.40
-0.27
-0.78
-3.04
-1.30
-0.46
-0.40
-0.27
-0.78
-4.14
-1.61
-0.94
-0.94
-0.79
-1.20
-3.97
-1.56
-0.90
-0.90
-0.76
-1.16
-4.50
-4.30
-6.10
-5.00
-4.10
-6.60
-4.50
-4.50
-3.78
-7.27
-6.48
-4.76
-7.82
-4.94
-4.50
-3.78
-7.27
-6.48
-4.76
-7.82
-4.94
-3.77
-3.24
-6.33
-5.11
-3.45
-6.76
-4.28
-4.47
-3.96
-6.08
-5.69
-4.03
-6.49
-4.97
-4.00
-3.20
-3.50
-3.40
-5.07
-3.48
-4.48
-3.76
-5.07
-3.48
-4.48
-3.76
-5.78
-3.70
-4.60
-3.98
-5.38
-3.44
-4.27
-3.71
-3.60
-3.30
-2.90
-3.40
-3.90
-4.50
-2.51
-1.87
-1.87
-1.74
-3.30
-2.54
-2.51
-1.87
-1.87
-1.74
-3.30
-2.54
-3.32
-2.68
-2.79
-2.66
-3.97
-3.15
-3.25
-2.61
-2.88
-2.65
-3.84
-3.12
-6.70
-6.50
-6.40
-7.00
-7.72
-6.79
-6.36
-6.09
-7.72
-6.79
-6.36
-6.10
-5.69
-5.03
-4.62
-4.36
-4.46
-4.05
-3.66
-3.40
-2.55
-3.10
-3.30
-2.20
-2.60
-2.90
-2.97
-3.65
-4.36
-4.46
-2.87
-3.23
-2.97
-3.65
-4.36
-4.46
-2.87
-3.23
-3.12
-3.79
-4.23
-4.88
-2.95
-3.39
-2.65
-3.30
-3.63
-4.52
-2.54
-2.92
-4.80
-5.05
-2.45
-1.60
-2.00
-3.50
-4.58
-5.62
-3.77
-1.48
-1.70
-2.50
-4.58
-5.62
-3.77
-1.48
-1.70
-2.50
-4.49
-5.23
-3.88
-1.77
-1.92
-2.69
-5.02
-5.12
-3.96
-2.29
-2.39
-3.13
2
Table 3: Dataset - Training III
Compound
Aliphatic amines
ammonia
azetidine
diethylamine
dimethylamine
dipropylamine
nbutylamine
npropylamine
piperazine
pyrrolidine
trimethylamine
Aromatic amines
2,4-dimethylpyridine
2,6-dimethylpyridine
2-ethylpyrazine
2-methylpyrazine
4-methylpyridine
pyridine
Nitriles
acetonitrile
benzonitrile
propionitrile
Amides
acetamide
N-methylacetamide
propionamide
Sulfurs
benzenethiol
diethylsulfide
dimethyldisulfide
ethanethiol
methanethiol
thioanisole
Multifunctionals
1-methylthymine
2-methoxyethanol
4-amino-3,5,6-trichloro
-2-carboxy-pyridine
9-methyladenine
morpholine
N-methylmorpholine
p-hydroxybenzaldehyde
Exp
PDAnum-1
PDAnum-2
PDAexp-1
PDAexp-2
-4.30
-5.60
-4.10
-4.30
-3.70
-4.30
-4.40
-7.40
-5.50
-3.20
-10.42
-3.57
-1.35
-3.36
-0.59
-4.09
-4.35
-6.21
-2.26
-1.34
-10.42
-3.57
-1.35
-3.36
-0.59
-4.09
-4.35
-6.21
-2.26
-1.34
-6.01
-4.00
-2.40
-3.85
-1.65
-2.99
-3.23
-7.37
-3.15
-3.54
-6.04
-4.08
-2.55
-4.03
-1.80
-3.08
-3.32
-7.12
-3.21
-3.75
-4.90
-4.60
-5.50
-5.60
-4.90
-4.70
-3.99
-3.71
-7.94
-8.66
-4.68
-5.14
-3.99
-3.71
-7.94
-8.66
-4.68
-5.14
-4.27
-4.00
-7.24
-7.81
-4.79
-5.16
-4.08
-3.83
-6.68
-7.25
-4.61
-4.98
-3.90
-4.10
-3.90
-5.80
-5.36
-4.68
-5.80
-5.36
-4.68
-4.64
-4.52
-3.56
-4.57
-4.39
-3.48
-9.70
-10.10
-9.40
-8.64
-6.86
-7.43
-8.64
-6.86
-7.43
-8.58
-7.40
-7.64
-7.96
-7.03
-7.14
-2.55
-1.30
-1.80
-1.30
-1.20
-2.70
-2.58
-0.18
-1.90
-1.67
-2.13
-1.87
-2.58
-0.18
-1.90
-1.67
-2.13
-1.87
-2.43
-0.11
-1.33
-1.26
-1.63
-1.92
-2.35
-0.14
-1.32
-1.26
-1.63
-1.86
-10.40
-6.80
-12.00
-11.73
-8.85
-14.45
-11.73
-8.85
-14.18
-11.12
-7.31
-9.19
-10.30
-7.69
-7.95
-13.60
-7.20
-6.30
-10.50
-19.91
-5.87
-3.95
-11.18
-19.07
-5.87
-3.95
-11.18
-14.17
-6.13
-5.82
-10.57
-15.25
-6.01
-5.72
-9.75
3
Table 4: Dataset - Training IV
Compound
Halides
trifluoroethanol
1,1-difluoroethane
1-bromobutane
1-chlorobutane
1-iodopentane
2-bromopropane
2-chloropropane
bromoethane
chlorobenzne
fluorobenzene
fluoroform
hexafluoropropane
iodobenzene
iodoethane
methyliodide
o-chlorotoluene
p-bromotoluene
p-dichlorobenzene
trichloromethane
Nitro
1-nitrobutane
1-nitropropane
2-methyl-1-nitrobenzene
nitroethane
Charged oxygen
acetate
propionate
Charged Nitrogen
ammonium
anilinium
pyridinium
methylammonium
nbutylammonium
N,N-dimethylanilinium
piperidinium
tbutylammonium
trimethylammonium
Charged Sulfur
thiophenolate
propanethiolate
(CH3)2 SH+
Exp
PDAnum-1
PDAnum-2
PDAexp-1
PDAexp-2
-4.30
-0.10
-0.40
-0.10
-0.10
-0.50
-0.25
-0.70
-1.10
-0.80
-0.80
3.90
-1.70
-0.70
-0.90
-1.15
-1.40
-1.00
-1.10
-8.57
-1.71
0.25
-0.01
-0.64
-0.11
-0.36
-0.38
-1.30
-0.91
-4.12
0.06
-1.40
-1.58
-2.17
-0.90
-0.85
-1.21
-1.87
-8.57
-1.71
0.25
-0.01
-0.64
-0.11
-0.36
-0.38
-1.30
-0.91
-4.12
0.06
-1.40
-1.58
-2.17
-0.90
-0.85
-1.21
-1.87
-4.86
-1.01
0.53
0.26
-0.22
0.13
-0.13
-0.13
-1.23
-0.82
-1.52
4.33
-1.21
-1.19
-1.67
-0.90
-0.81
-0.89
-0.91
-3.68
-0.91
0.54
0.27
-0.20
0.14
-0.13
-0.12
-1.14
-0.74
-1.11
4.67
-1.12
-1.16
-1.64
-0.82
-0.71
-0.78
-0.72
-3.10
-3.30
-3.60
-3.70
-1.60
-1.90
-2.64
-2.35
-1.77
-2.06
-2.80
-2.52
-1.08
-1.39
-2.55
-1.85
-0.85
-1.16
-2.41
-1.59
-80.0
-79.0
-79.42
-76.86
-82.33
-79.73
-80.54
-78.78
-81.02
-79.47
-86.0
-66.0
-59.0
-71.0
-66.0
-52.0
-60.0
-63.0
-57.0
-87.89
-63.57
-57.18
-74.81
-65.58
-50.98
-56.34
-61.58
-59.02
-88.45
-63.38
-57.18
-74.77
-65.67
-50.55
-56.11
-61.84
-58.54
-87.20
-63.20
-56.57
-74.50
-65.58
-51.51
-56.27
-61.84
-59.14
-86.06
-63.43
-55.66
-74.24
-65.06
-52.17
-56.33
-61.02
-59.77
-67.0
-76.0
-61.0
-69.49
-78.35
-62.94
-69.49
-78.35
-62.94
-67.74
-75.33
-61.27
-67.55
-75.49
-61.01
4
Table 5: Dataset - Validation I
Compound
Linear Alkanes
methane
pentane
Branched Alkanes
isobutane
Cycloalkanes
cyclopentane
Alkenes
ethylene
1-propene
Alkynes
1-pentyne
Arenes
naphtalene
phenanthrene
Alcohols
methanol
nbutanol
npropanol
Aldehydes
octanal
pentanal
Ketones
4-heptanone
acetophenone
Carboxylic Acids
hexanoic acid
Esters
methylbutanoate
methylpropanoate
Ethers
dimethylether
methylpropylether
Aliphatic amines
ethylamine
methylamine
piperidine
Aromatic amines
2-methylpyridine
aniline
Nitriles
butanonitrile
Amides
N,N-dimethylacetamide
Sulfurs
hydrogensulfide
methylethylsulfide
Exp
PDAnum-1
PDAnum-2
PDAexp-1
PDAexp-2
2.00
2.30
1.15
2.05
1.15
2.05
1.30
2.24
1.30
2.23
2.30
1.78
1.78
1.95
1.94
1.20
1.78
1.78
1.88
1.87
1.30
1.30
0.33
0.71
0.33
0.71
0.62
0.89
0.61
0.87
0.00
0.53
0.53
0.77
0.77
-2.40
-3.95
-2.27
-3.07
-2.27
-3.07
-3.00
-4.14
-2.89
-3.98
-5.10
-4.70
-4.80
-7.55
-5.74
-6.01
-7.55
-5.74
-6.01
-5.79
-4.42
-4.68
-6.33
-5.00
-5.26
-2.30
-3.00
-2.29
-3.22
-2.29
-3.22
-2.49
-3.44
-2.25
-3.18
-2.90
-4.60
-1.01
-4.20
-1.01
-4.20
-1.93
-5.39
-1.92
-5.20
-6.20
-5.83
-5.83
-4.10
-3.14
-2.80
-2.90
-3.16
-3.56
-3.16
-3.56
-3.25
-3.64
-2.83
-3.20
-1.90
-1.70
-2.94
-1.79
-2.94
-1.79
-2.77
-1.85
-3.24
-2.35
-4.50
-4.60
-5.10
-4.76
-6.26
-1.53
-4.76
-6.26
-1.53
-3.57
-4.66
-2.67
-3.66
-4.78
-2.72
-4.80
-4.90
-4.44
-5.63
-4.44
-4.73
-4.64
-5.03
-4.44
-8.47
-3.60
-4.41
-4.41
-3.28
-3.20
-8.50
-5.03
-5.03
-5.92
-5.90
-0.70
-1.40
-3.96
-0.60
-3.96
-0.60
-3.01
-0.43
-2.98
-0.46
5
Table 6: Dataset - Validation II
Compound
Multifunctionals
butenyne
m-hydroxybenzaldehyde
p-bromophenol
Halides
2-iodopropane
bromobenzene
chloroethane
chlorofluoromethane
dibromomethane
fluoromethane
tetrafluoromethane
Nitro
2-nitropropane
nitrobenzene
Charged Oxygen
benzoate
Charged Nitrogen
dimethylammonium
npropylammonium
tetramethylammonium
Charged sulfur
CH3(SH2 )+
Exp
PDAnum-1
PDAnum-2
PDAexp-1
PDAexp-2
0.00
-9.50
-7.10
-1.16
-10.87
-7.63
-1.16
-10.87
-7.63
-0.89
-10.14
-6.20
-0.87
-9.33
-5.75
-0.50
-1.50
-0.60
-0.80
-2.10
-0.20
3.20
-1.10
-1.34
-0.66
-2.91
-1.29
-1.06
-1.53
-1.10
-1.34
-0.66
-2.91
-1.29
-1.06
-1.53
-0.78
-1.22
-0.40
-1.77
-0.74
-0.66
1.022
-0.77
-1.12
-0.39
-1.62
-0.65
-0.65
1.33
-3.10
-4.10
-1.82
-3.17
-1.99
-3.33
-1.46
-2.90
-1.36
-2.65
-76.0
-71.47
-74.08
-74.11
-74.52
-64.0
-67.0
-52.0
-65.52
-66.82
-54.64
-65.16
-66.92
-54.15
-65.46
-66.85
-54.91
-65.77
-66.34
-55.71
-61.0
-75.49
-75.50
-72.44
-72.04
6
II : Potentials of Mean Force of systems reported in table 8 and 9 of the
main article
1
Free energy / kcal.mol
-1
0.75
Vacuum
PDAnum-1
PDAexp-2
PDAexp-1
0.5
0.25
0
-0.25
-0.5
-0.75
-1
3.5
4
4.5
5
5.5 6 6.5 7
C-C distance / Å
7.5
8
8.5
9
Figure 1: Potential of mean force Methane-Methane
2
-1
1.5
Free energy / kcal.mol
2
Vacuum
PDAnum-1
PDAexp-2
PDAexp-1
1
0.5
0
-0.5
-1
-1.5
-2
4
4.5
5
5.5 6 6.5 7 7.5 8 8.5
center-center distance / Å
9
9.5 10 10.5
Figure 2: Potential of mean force Benzene-Benzene
7
10
Free energy / kcal.mol
-1
8
6
PDAnum-1
PDAnum-2
PDAexp-1
PDAexp-2
4
2
0
-2
5
6
7
C-C distance / Å
8
9
Figure 3: Potential of mean force Arg+ Arg+, planar
2
1.5
Free energy / kcal.mol
-1
1
0.5
0
-0.5
PDAnum-1
PDAnum-2
PDAexp-1
PDAexp-2
-1
-1.5
-2
-2.5
3
4
5
7
6
C-C distance / Å
8
9
10
Figure 4: Potential of mean force Arg+ Arg+, stacked
2
Free energy / kcal.mol
-1
0
-2
PDAnum-1
PDAexp-1
PDAexp-2
-4
-6
-8
-10
4
5
6
7
C-C distance / Å
8
9
Figure 5: Potential of mean force Glu0 Glu0, planar
8
10
Free energy / kcal.mol
-1
8
6
PDAnum-1
PDAnum-2
PDAexp-1
PDAexp-2
4
2
0
-2
4
7
6
C-C distance / Å
5
8
9
Figure 6: Potential of mean force Glu- Glu-, planar
2
Free energy / kcal.mol
-1
1
0
-1
PDAnum-1
PDAnum-2
PDAexp-1
PDAexp-2
-2
-3
-4
-5
3
4
5
N-O distance / Å
7
6
Figure 7: Potential of mean force HisD Glu-, planar
2
Free energy / kcal.mol
-1
1
0
PDAnum-1
PDAexp-1
PDAexp-2
-1
-2
-3
-4
3
4
5
N-N distance / Å
6
7
Figure 8: Potential of mean force HisD HisE, planar
9
1
Free energy / kcal.mol
-1
0
-1
-2
PDAnum-1
PDAnum-2
PDAexp-1
PDAexp-2
-3
-4
-5
-6
-7
3
4
5
N-O distance / Å
6
7
Figure 9: Potential of mean force HisP Glu-, planar
2
Free energy / kcal.mol
-1
1
0
-1
PDAnum-1
PDAexp-1
PDAexp-2
-2
-3
-4
-5
-6
3
4
5
N-N distance / Å
6
7
Figure 10: Potential of mean force HisP HisE, planar
4
Free energy / kcal.mol
-1
3
2
PDAnum-1
PDAexp-1
PDAexp-2
1
0
-1
-2
4
5
6
7
N-N distance / Å
8
9
Figure 11: Potential of mean force HisP HisP, planar
10
Free energy / kcal.mol
-1
2
1
0
PDAnum-1
PDAexp-1
PDAexp-2
-1
-2
-3
3
4
5
6
center-center distance / Å
7
8
Figure 12: Potential of mean force HisP HisP, stacked
2
Free energy / kcal.mol
-1
1
0
PDAnum-1
PDAnum-2
PDAexp-1
PDAexp-2
-1
-2
-3
-4
3
4
5
6
N-C distance / Å
7
Figure 13: Potential of mean force Lys+ Glu-, planar
11
❡❧s ✉s✐♥❣ t❤❡ P❛✐r✇✐s❡ ❉❡s❝r❡❡♥✐♥❣ ❆♣♣r♦①✐♠❛t✐♦♥
Julien Michel, Jonathan W. Essex
School of Chemistry, University of Southampton, Highfield, Southampton, SO17 1BJ, UK
Richard D. Taylor
Astex Technology Ltd, 436 Cambridge Science Park, Milton Road Cambridge, CB4 0QA, UK
Supplementary Information
1
I : Experimental and Predicted Free energies of hydration for the four
different GBSA models
Energies are in kcal.mol−1 .
Table 1: Dataset - Training I
Compound
Linear Alkanes
ethane
propane
butane
hexane
heptane
octane
Branched Alkanes
2-methylpentane
2,4-dimethylpentane
neopentane
Cycloalkanes
cyclopropane
cyclohexane
methyl-cyclohexane
cis-1,2-dimethylcyclohexane
Alkenes
2-methylpropene
1-butene
cyclopentene
(E)2-pentene
1-pentene
trans-1,3-butadiene
Alkynes
propyne
1-butyne
1-hexyne
Exp
PDAnum-1
PDAnum-2
PDAexp-1
PDAexp-2
1.80
2.00
2.20
2.50
2.60
2.90
1.39
1.60
1.82
2.28
2.51
2.74
1.39
1.60
1.82
2.28
2.28
2.74
1.57
1.79
2.01
2.47
2.71
2.94
1.57
1.78
2.00
2.45
2.68
2.91
2.50
2.90
2.50
2.15
2.37
1.94
2.15
2.37
1.94
2.36
2.49
2.06
2.35
2.47
2.04
0.80
1.20
1.70
1.60
1.12
2.00
2.22
2.36
1.12
2.00
2.22
2.36
1.26
2.06
2.26
2.35
1.24
2.05
2.24
2.33
1.20
1.40
0.60
1.30
1.70
0.60
1.03
1.03
0.88
1.45
1.28
0.03
1.03
1.03
0.88
1.45
1.28
0.03
1.11
1.19
0.80
1.51
1.41
0.21
1.09
1.17
0.79
1.47
1.38
0.19
-0.30
-0.20
0.30
-0.19
0.22
0.77
-0.19
0.22
0.77
0.07
0.46
1.02
0.07
0.46
1.01
1
Table 2: Dataset - Training II
Compound
Arenes
anthracene
benzene
ethylbenzene
o-xylene
m-xylene
toluene
Alcohols
2-butanol
3-pentanol
4-methylphenol
ethanol
1-octanol
phenol
t-butanol
Aldehydes
benzaldehyde
butanal
ethanal
propanal
Ketones
2-butanone
2-hexanone
3,3-dimethylbutanone
3-pentanone
acetone
cyclopentanone
Carboxylic Acids
acetic acid
propanoic acid
butanoic acid
pentanoic acid
Esters
butylacetate
ethylacetate
methylacetate
methylbenzoate
methylpentanoate
propylacetate
Ethers
1,2-dimethoxyethane
1,4-dioxane
anisole
diethylether
methylisopropylether
Tetrahydrofuran
Exp
PDAnum-1
PDAnum-2
PDAexp-1
PDAexp-2
-4.20
-0.90
-0.80
-0.90
-0.80
-0.90
-3.04
-1.30
-0.46
-0.40
-0.27
-0.78
-3.04
-1.30
-0.46
-0.40
-0.27
-0.78
-4.14
-1.61
-0.94
-0.94
-0.79
-1.20
-3.97
-1.56
-0.90
-0.90
-0.76
-1.16
-4.50
-4.30
-6.10
-5.00
-4.10
-6.60
-4.50
-4.50
-3.78
-7.27
-6.48
-4.76
-7.82
-4.94
-4.50
-3.78
-7.27
-6.48
-4.76
-7.82
-4.94
-3.77
-3.24
-6.33
-5.11
-3.45
-6.76
-4.28
-4.47
-3.96
-6.08
-5.69
-4.03
-6.49
-4.97
-4.00
-3.20
-3.50
-3.40
-5.07
-3.48
-4.48
-3.76
-5.07
-3.48
-4.48
-3.76
-5.78
-3.70
-4.60
-3.98
-5.38
-3.44
-4.27
-3.71
-3.60
-3.30
-2.90
-3.40
-3.90
-4.50
-2.51
-1.87
-1.87
-1.74
-3.30
-2.54
-2.51
-1.87
-1.87
-1.74
-3.30
-2.54
-3.32
-2.68
-2.79
-2.66
-3.97
-3.15
-3.25
-2.61
-2.88
-2.65
-3.84
-3.12
-6.70
-6.50
-6.40
-7.00
-7.72
-6.79
-6.36
-6.09
-7.72
-6.79
-6.36
-6.10
-5.69
-5.03
-4.62
-4.36
-4.46
-4.05
-3.66
-3.40
-2.55
-3.10
-3.30
-2.20
-2.60
-2.90
-2.97
-3.65
-4.36
-4.46
-2.87
-3.23
-2.97
-3.65
-4.36
-4.46
-2.87
-3.23
-3.12
-3.79
-4.23
-4.88
-2.95
-3.39
-2.65
-3.30
-3.63
-4.52
-2.54
-2.92
-4.80
-5.05
-2.45
-1.60
-2.00
-3.50
-4.58
-5.62
-3.77
-1.48
-1.70
-2.50
-4.58
-5.62
-3.77
-1.48
-1.70
-2.50
-4.49
-5.23
-3.88
-1.77
-1.92
-2.69
-5.02
-5.12
-3.96
-2.29
-2.39
-3.13
2
Table 3: Dataset - Training III
Compound
Aliphatic amines
ammonia
azetidine
diethylamine
dimethylamine
dipropylamine
nbutylamine
npropylamine
piperazine
pyrrolidine
trimethylamine
Aromatic amines
2,4-dimethylpyridine
2,6-dimethylpyridine
2-ethylpyrazine
2-methylpyrazine
4-methylpyridine
pyridine
Nitriles
acetonitrile
benzonitrile
propionitrile
Amides
acetamide
N-methylacetamide
propionamide
Sulfurs
benzenethiol
diethylsulfide
dimethyldisulfide
ethanethiol
methanethiol
thioanisole
Multifunctionals
1-methylthymine
2-methoxyethanol
4-amino-3,5,6-trichloro
-2-carboxy-pyridine
9-methyladenine
morpholine
N-methylmorpholine
p-hydroxybenzaldehyde
Exp
PDAnum-1
PDAnum-2
PDAexp-1
PDAexp-2
-4.30
-5.60
-4.10
-4.30
-3.70
-4.30
-4.40
-7.40
-5.50
-3.20
-10.42
-3.57
-1.35
-3.36
-0.59
-4.09
-4.35
-6.21
-2.26
-1.34
-10.42
-3.57
-1.35
-3.36
-0.59
-4.09
-4.35
-6.21
-2.26
-1.34
-6.01
-4.00
-2.40
-3.85
-1.65
-2.99
-3.23
-7.37
-3.15
-3.54
-6.04
-4.08
-2.55
-4.03
-1.80
-3.08
-3.32
-7.12
-3.21
-3.75
-4.90
-4.60
-5.50
-5.60
-4.90
-4.70
-3.99
-3.71
-7.94
-8.66
-4.68
-5.14
-3.99
-3.71
-7.94
-8.66
-4.68
-5.14
-4.27
-4.00
-7.24
-7.81
-4.79
-5.16
-4.08
-3.83
-6.68
-7.25
-4.61
-4.98
-3.90
-4.10
-3.90
-5.80
-5.36
-4.68
-5.80
-5.36
-4.68
-4.64
-4.52
-3.56
-4.57
-4.39
-3.48
-9.70
-10.10
-9.40
-8.64
-6.86
-7.43
-8.64
-6.86
-7.43
-8.58
-7.40
-7.64
-7.96
-7.03
-7.14
-2.55
-1.30
-1.80
-1.30
-1.20
-2.70
-2.58
-0.18
-1.90
-1.67
-2.13
-1.87
-2.58
-0.18
-1.90
-1.67
-2.13
-1.87
-2.43
-0.11
-1.33
-1.26
-1.63
-1.92
-2.35
-0.14
-1.32
-1.26
-1.63
-1.86
-10.40
-6.80
-12.00
-11.73
-8.85
-14.45
-11.73
-8.85
-14.18
-11.12
-7.31
-9.19
-10.30
-7.69
-7.95
-13.60
-7.20
-6.30
-10.50
-19.91
-5.87
-3.95
-11.18
-19.07
-5.87
-3.95
-11.18
-14.17
-6.13
-5.82
-10.57
-15.25
-6.01
-5.72
-9.75
3
Table 4: Dataset - Training IV
Compound
Halides
trifluoroethanol
1,1-difluoroethane
1-bromobutane
1-chlorobutane
1-iodopentane
2-bromopropane
2-chloropropane
bromoethane
chlorobenzne
fluorobenzene
fluoroform
hexafluoropropane
iodobenzene
iodoethane
methyliodide
o-chlorotoluene
p-bromotoluene
p-dichlorobenzene
trichloromethane
Nitro
1-nitrobutane
1-nitropropane
2-methyl-1-nitrobenzene
nitroethane
Charged oxygen
acetate
propionate
Charged Nitrogen
ammonium
anilinium
pyridinium
methylammonium
nbutylammonium
N,N-dimethylanilinium
piperidinium
tbutylammonium
trimethylammonium
Charged Sulfur
thiophenolate
propanethiolate
(CH3)2 SH+
Exp
PDAnum-1
PDAnum-2
PDAexp-1
PDAexp-2
-4.30
-0.10
-0.40
-0.10
-0.10
-0.50
-0.25
-0.70
-1.10
-0.80
-0.80
3.90
-1.70
-0.70
-0.90
-1.15
-1.40
-1.00
-1.10
-8.57
-1.71
0.25
-0.01
-0.64
-0.11
-0.36
-0.38
-1.30
-0.91
-4.12
0.06
-1.40
-1.58
-2.17
-0.90
-0.85
-1.21
-1.87
-8.57
-1.71
0.25
-0.01
-0.64
-0.11
-0.36
-0.38
-1.30
-0.91
-4.12
0.06
-1.40
-1.58
-2.17
-0.90
-0.85
-1.21
-1.87
-4.86
-1.01
0.53
0.26
-0.22
0.13
-0.13
-0.13
-1.23
-0.82
-1.52
4.33
-1.21
-1.19
-1.67
-0.90
-0.81
-0.89
-0.91
-3.68
-0.91
0.54
0.27
-0.20
0.14
-0.13
-0.12
-1.14
-0.74
-1.11
4.67
-1.12
-1.16
-1.64
-0.82
-0.71
-0.78
-0.72
-3.10
-3.30
-3.60
-3.70
-1.60
-1.90
-2.64
-2.35
-1.77
-2.06
-2.80
-2.52
-1.08
-1.39
-2.55
-1.85
-0.85
-1.16
-2.41
-1.59
-80.0
-79.0
-79.42
-76.86
-82.33
-79.73
-80.54
-78.78
-81.02
-79.47
-86.0
-66.0
-59.0
-71.0
-66.0
-52.0
-60.0
-63.0
-57.0
-87.89
-63.57
-57.18
-74.81
-65.58
-50.98
-56.34
-61.58
-59.02
-88.45
-63.38
-57.18
-74.77
-65.67
-50.55
-56.11
-61.84
-58.54
-87.20
-63.20
-56.57
-74.50
-65.58
-51.51
-56.27
-61.84
-59.14
-86.06
-63.43
-55.66
-74.24
-65.06
-52.17
-56.33
-61.02
-59.77
-67.0
-76.0
-61.0
-69.49
-78.35
-62.94
-69.49
-78.35
-62.94
-67.74
-75.33
-61.27
-67.55
-75.49
-61.01
4
Table 5: Dataset - Validation I
Compound
Linear Alkanes
methane
pentane
Branched Alkanes
isobutane
Cycloalkanes
cyclopentane
Alkenes
ethylene
1-propene
Alkynes
1-pentyne
Arenes
naphtalene
phenanthrene
Alcohols
methanol
nbutanol
npropanol
Aldehydes
octanal
pentanal
Ketones
4-heptanone
acetophenone
Carboxylic Acids
hexanoic acid
Esters
methylbutanoate
methylpropanoate
Ethers
dimethylether
methylpropylether
Aliphatic amines
ethylamine
methylamine
piperidine
Aromatic amines
2-methylpyridine
aniline
Nitriles
butanonitrile
Amides
N,N-dimethylacetamide
Sulfurs
hydrogensulfide
methylethylsulfide
Exp
PDAnum-1
PDAnum-2
PDAexp-1
PDAexp-2
2.00
2.30
1.15
2.05
1.15
2.05
1.30
2.24
1.30
2.23
2.30
1.78
1.78
1.95
1.94
1.20
1.78
1.78
1.88
1.87
1.30
1.30
0.33
0.71
0.33
0.71
0.62
0.89
0.61
0.87
0.00
0.53
0.53
0.77
0.77
-2.40
-3.95
-2.27
-3.07
-2.27
-3.07
-3.00
-4.14
-2.89
-3.98
-5.10
-4.70
-4.80
-7.55
-5.74
-6.01
-7.55
-5.74
-6.01
-5.79
-4.42
-4.68
-6.33
-5.00
-5.26
-2.30
-3.00
-2.29
-3.22
-2.29
-3.22
-2.49
-3.44
-2.25
-3.18
-2.90
-4.60
-1.01
-4.20
-1.01
-4.20
-1.93
-5.39
-1.92
-5.20
-6.20
-5.83
-5.83
-4.10
-3.14
-2.80
-2.90
-3.16
-3.56
-3.16
-3.56
-3.25
-3.64
-2.83
-3.20
-1.90
-1.70
-2.94
-1.79
-2.94
-1.79
-2.77
-1.85
-3.24
-2.35
-4.50
-4.60
-5.10
-4.76
-6.26
-1.53
-4.76
-6.26
-1.53
-3.57
-4.66
-2.67
-3.66
-4.78
-2.72
-4.80
-4.90
-4.44
-5.63
-4.44
-4.73
-4.64
-5.03
-4.44
-8.47
-3.60
-4.41
-4.41
-3.28
-3.20
-8.50
-5.03
-5.03
-5.92
-5.90
-0.70
-1.40
-3.96
-0.60
-3.96
-0.60
-3.01
-0.43
-2.98
-0.46
5
Table 6: Dataset - Validation II
Compound
Multifunctionals
butenyne
m-hydroxybenzaldehyde
p-bromophenol
Halides
2-iodopropane
bromobenzene
chloroethane
chlorofluoromethane
dibromomethane
fluoromethane
tetrafluoromethane
Nitro
2-nitropropane
nitrobenzene
Charged Oxygen
benzoate
Charged Nitrogen
dimethylammonium
npropylammonium
tetramethylammonium
Charged sulfur
CH3(SH2 )+
Exp
PDAnum-1
PDAnum-2
PDAexp-1
PDAexp-2
0.00
-9.50
-7.10
-1.16
-10.87
-7.63
-1.16
-10.87
-7.63
-0.89
-10.14
-6.20
-0.87
-9.33
-5.75
-0.50
-1.50
-0.60
-0.80
-2.10
-0.20
3.20
-1.10
-1.34
-0.66
-2.91
-1.29
-1.06
-1.53
-1.10
-1.34
-0.66
-2.91
-1.29
-1.06
-1.53
-0.78
-1.22
-0.40
-1.77
-0.74
-0.66
1.022
-0.77
-1.12
-0.39
-1.62
-0.65
-0.65
1.33
-3.10
-4.10
-1.82
-3.17
-1.99
-3.33
-1.46
-2.90
-1.36
-2.65
-76.0
-71.47
-74.08
-74.11
-74.52
-64.0
-67.0
-52.0
-65.52
-66.82
-54.64
-65.16
-66.92
-54.15
-65.46
-66.85
-54.91
-65.77
-66.34
-55.71
-61.0
-75.49
-75.50
-72.44
-72.04
6
II : Potentials of Mean Force of systems reported in table 8 and 9 of the
main article
1
Free energy / kcal.mol
-1
0.75
Vacuum
PDAnum-1
PDAexp-2
PDAexp-1
0.5
0.25
0
-0.25
-0.5
-0.75
-1
3.5
4
4.5
5
5.5 6 6.5 7
C-C distance / Å
7.5
8
8.5
9
Figure 1: Potential of mean force Methane-Methane
2
-1
1.5
Free energy / kcal.mol
2
Vacuum
PDAnum-1
PDAexp-2
PDAexp-1
1
0.5
0
-0.5
-1
-1.5
-2
4
4.5
5
5.5 6 6.5 7 7.5 8 8.5
center-center distance / Å
9
9.5 10 10.5
Figure 2: Potential of mean force Benzene-Benzene
7
10
Free energy / kcal.mol
-1
8
6
PDAnum-1
PDAnum-2
PDAexp-1
PDAexp-2
4
2
0
-2
5
6
7
C-C distance / Å
8
9
Figure 3: Potential of mean force Arg+ Arg+, planar
2
1.5
Free energy / kcal.mol
-1
1
0.5
0
-0.5
PDAnum-1
PDAnum-2
PDAexp-1
PDAexp-2
-1
-1.5
-2
-2.5
3
4
5
7
6
C-C distance / Å
8
9
10
Figure 4: Potential of mean force Arg+ Arg+, stacked
2
Free energy / kcal.mol
-1
0
-2
PDAnum-1
PDAexp-1
PDAexp-2
-4
-6
-8
-10
4
5
6
7
C-C distance / Å
8
9
Figure 5: Potential of mean force Glu0 Glu0, planar
8
10
Free energy / kcal.mol
-1
8
6
PDAnum-1
PDAnum-2
PDAexp-1
PDAexp-2
4
2
0
-2
4
7
6
C-C distance / Å
5
8
9
Figure 6: Potential of mean force Glu- Glu-, planar
2
Free energy / kcal.mol
-1
1
0
-1
PDAnum-1
PDAnum-2
PDAexp-1
PDAexp-2
-2
-3
-4
-5
3
4
5
N-O distance / Å
7
6
Figure 7: Potential of mean force HisD Glu-, planar
2
Free energy / kcal.mol
-1
1
0
PDAnum-1
PDAexp-1
PDAexp-2
-1
-2
-3
-4
3
4
5
N-N distance / Å
6
7
Figure 8: Potential of mean force HisD HisE, planar
9
1
Free energy / kcal.mol
-1
0
-1
-2
PDAnum-1
PDAnum-2
PDAexp-1
PDAexp-2
-3
-4
-5
-6
-7
3
4
5
N-O distance / Å
6
7
Figure 9: Potential of mean force HisP Glu-, planar
2
Free energy / kcal.mol
-1
1
0
-1
PDAnum-1
PDAexp-1
PDAexp-2
-2
-3
-4
-5
-6
3
4
5
N-N distance / Å
6
7
Figure 10: Potential of mean force HisP HisE, planar
4
Free energy / kcal.mol
-1
3
2
PDAnum-1
PDAexp-1
PDAexp-2
1
0
-1
-2
4
5
6
7
N-N distance / Å
8
9
Figure 11: Potential of mean force HisP HisP, planar
10
Free energy / kcal.mol
-1
2
1
0
PDAnum-1
PDAexp-1
PDAexp-2
-1
-2
-3
3
4
5
6
center-center distance / Å
7
8
Figure 12: Potential of mean force HisP HisP, stacked
2
Free energy / kcal.mol
-1
1
0
PDAnum-1
PDAnum-2
PDAexp-1
PDAexp-2
-1
-2
-3
-4
3
4
5
6
N-C distance / Å
7
Figure 13: Potential of mean force Lys+ Glu-, planar
11