suppmat_1760. 101KB Jun 05 2011 09:30:56 PM

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❚❤❡ 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 Exp PDAnum-1 PDAnum-2 PDAexp-1 PDAexp-2 Linear Alkanes

ethane 1.80 1.39 1.39 1.57 1.57

propane 2.00 1.60 1.60 1.79 1.78

butane 2.20 1.82 1.82 2.01 2.00

hexane 2.50 2.28 2.28 2.47 2.45

heptane 2.60 2.51 2.28 2.71 2.68

octane 2.90 2.74 2.74 2.94 2.91

Branched Alkanes

2-methylpentane 2.50 2.15 2.15 2.36 2.35

2,4-dimethylpentane 2.90 2.37 2.37 2.49 2.47

neopentane 2.50 1.94 1.94 2.06 2.04

Cycloalkanes

cyclopropane 0.80 1.12 1.12 1.26 1.24

cyclohexane 1.20 2.00 2.00 2.06 2.05

methyl-cyclohexane 1.70 2.22 2.22 2.26 2.24 cis-1,2-dimethylcyclohexane 1.60 2.36 2.36 2.35 2.33

Alkenes

2-methylpropene 1.20 1.03 1.03 1.11 1.09

1-butene 1.40 1.03 1.03 1.19 1.17

cyclopentene 0.60 0.88 0.88 0.80 0.79

(E)2-pentene 1.30 1.45 1.45 1.51 1.47

1-pentene 1.70 1.28 1.28 1.41 1.38

trans-1,3-butadiene 0.60 0.03 0.03 0.21 0.19 Alkynes

propyne -0.30 -0.19 -0.19 0.07 0.07

1-butyne -0.20 0.22 0.22 0.46 0.46

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Table 2: Dataset - Training II

Compound Exp PDAnum-1 PDAnum-2 PDAexp-1 PDAexp-2 Arenes

anthracene -4.20 -3.04 -3.04 -4.14 -3.97

benzene -0.90 -1.30 -1.30 -1.61 -1.56

ethylbenzene -0.80 -0.46 -0.46 -0.94 -0.90 o-xylene -0.90 -0.40 -0.40 -0.94 -0.90 m-xylene -0.80 -0.27 -0.27 -0.79 -0.76 toluene -0.90 -0.78 -0.78 -1.20 -1.16 Alcohols

2-butanol -4.50 -4.50 -4.50 -3.77 -4.47 3-pentanol -4.30 -3.78 -3.78 -3.24 -3.96 4-methylphenol -6.10 -7.27 -7.27 -6.33 -6.08 ethanol -5.00 -6.48 -6.48 -5.11 -5.69 1-octanol -4.10 -4.76 -4.76 -3.45 -4.03

phenol -6.60 -7.82 -7.82 -6.76 -6.49

t-butanol -4.50 -4.94 -4.94 -4.28 -4.97 Aldehydes

benzaldehyde -4.00 -5.07 -5.07 -5.78 -5.38 butanal -3.20 -3.48 -3.48 -3.70 -3.44 ethanal -3.50 -4.48 -4.48 -4.60 -4.27 propanal -3.40 -3.76 -3.76 -3.98 -3.71

Ketones

2-butanone -3.60 -2.51 -2.51 -3.32 -3.25 2-hexanone -3.30 -1.87 -1.87 -2.68 -2.61 3,3-dimethylbutanone -2.90 -1.87 -1.87 -2.79 -2.88 3-pentanone -3.40 -1.74 -1.74 -2.66 -2.65 acetone -3.90 -3.30 -3.30 -3.97 -3.84 cyclopentanone -4.50 -2.54 -2.54 -3.15 -3.12 Carboxylic Acids

acetic acid -6.70 -7.72 -7.72 -5.69 -4.46 propanoic acid -6.50 -6.79 -6.79 -5.03 -4.05 butanoic acid -6.40 -6.36 -6.36 -4.62 -3.66 pentanoic acid -7.00 -6.09 -6.10 -4.36 -3.40

Esters

butylacetate -2.55 -2.97 -2.97 -3.12 -2.65 ethylacetate -3.10 -3.65 -3.65 -3.79 -3.30 methylacetate -3.30 -4.36 -4.36 -4.23 -3.63 methylbenzoate -2.20 -4.46 -4.46 -4.88 -4.52 methylpentanoate -2.60 -2.87 -2.87 -2.95 -2.54 propylacetate -2.90 -3.23 -3.23 -3.39 -2.92

Ethers

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Table 3: Dataset - Training III

Compound Exp PDAnum-1 PDAnum-2 PDAexp-1 PDAexp-2 Aliphatic amines

ammonia -4.30 -10.42 -10.42 -6.01 -6.04 azetidine -5.60 -3.57 -3.57 -4.00 -4.08 diethylamine -4.10 -1.35 -1.35 -2.40 -2.55 dimethylamine -4.30 -3.36 -3.36 -3.85 -4.03 dipropylamine -3.70 -0.59 -0.59 -1.65 -1.80 nbutylamine -4.30 -4.09 -4.09 -2.99 -3.08 npropylamine -4.40 -4.35 -4.35 -3.23 -3.32 piperazine -7.40 -6.21 -6.21 -7.37 -7.12 pyrrolidine -5.50 -2.26 -2.26 -3.15 -3.21 trimethylamine -3.20 -1.34 -1.34 -3.54 -3.75 Aromatic amines

2,4-dimethylpyridine -4.90 -3.99 -3.99 -4.27 -4.08 2,6-dimethylpyridine -4.60 -3.71 -3.71 -4.00 -3.83 2-ethylpyrazine -5.50 -7.94 -7.94 -7.24 -6.68 2-methylpyrazine -5.60 -8.66 -8.66 -7.81 -7.25 4-methylpyridine -4.90 -4.68 -4.68 -4.79 -4.61 pyridine -4.70 -5.14 -5.14 -5.16 -4.98

Nitriles

acetonitrile -3.90 -5.80 -5.80 -4.64 -4.57 benzonitrile -4.10 -5.36 -5.36 -4.52 -4.39 propionitrile -3.90 -4.68 -4.68 -3.56 -3.48

Amides

acetamide -9.70 -8.64 -8.64 -8.58 -7.96 N-methylacetamide -10.10 -6.86 -6.86 -7.40 -7.03 propionamide -9.40 -7.43 -7.43 -7.64 -7.14

Sulfurs

benzenethiol -2.55 -2.58 -2.58 -2.43 -2.35 diethylsulfide -1.30 -0.18 -0.18 -0.11 -0.14 dimethyldisulfide -1.80 -1.90 -1.90 -1.33 -1.32 ethanethiol -1.30 -1.67 -1.67 -1.26 -1.26 methanethiol -1.20 -2.13 -2.13 -1.63 -1.63 thioanisole -2.70 -1.87 -1.87 -1.92 -1.86 Multifunctionals

1-methylthymine -10.40 -11.73 -11.73 -11.12 -10.30 2-methoxyethanol -6.80 -8.85 -8.85 -7.31 -7.69 4-amino-3,5,6-trichloro -12.00 -14.45 -14.18 -9.19 -7.95

-2-carboxy-pyridine

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Table 4: Dataset - Training IV

Compound Exp PDAnum-1 PDAnum-2 PDAexp-1 PDAexp-2 Halides

trifluoroethanol -4.30 -8.57 -8.57 -4.86 -3.68 1,1-difluoroethane -0.10 -1.71 -1.71 -1.01 -0.91 1-bromobutane -0.40 0.25 0.25 0.53 0.54 1-chlorobutane -0.10 -0.01 -0.01 0.26 0.27 1-iodopentane -0.10 -0.64 -0.64 -0.22 -0.20 2-bromopropane -0.50 -0.11 -0.11 0.13 0.14 2-chloropropane -0.25 -0.36 -0.36 -0.13 -0.13

bromoethane -0.70 -0.38 -0.38 -0.13 -0.12 chlorobenzne -1.10 -1.30 -1.30 -1.23 -1.14 fluorobenzene -0.80 -0.91 -0.91 -0.82 -0.74 fluoroform -0.80 -4.12 -4.12 -1.52 -1.11 hexafluoropropane 3.90 0.06 0.06 4.33 4.67

iodobenzene -1.70 -1.40 -1.40 -1.21 -1.12 iodoethane -0.70 -1.58 -1.58 -1.19 -1.16 methyliodide -0.90 -2.17 -2.17 -1.67 -1.64 o-chlorotoluene -1.15 -0.90 -0.90 -0.90 -0.82 p-bromotoluene -1.40 -0.85 -0.85 -0.81 -0.71 p-dichlorobenzene -1.00 -1.21 -1.21 -0.89 -0.78 trichloromethane -1.10 -1.87 -1.87 -0.91 -0.72

Nitro

1-nitrobutane -3.10 -1.60 -1.77 -1.08 -0.85 1-nitropropane -3.30 -1.90 -2.06 -1.39 -1.16 2-methyl-1-nitrobenzene -3.60 -2.64 -2.80 -2.55 -2.41 nitroethane -3.70 -2.35 -2.52 -1.85 -1.59 Charged oxygen

acetate -80.0 -79.42 -82.33 -80.54 -81.02 propionate -79.0 -76.86 -79.73 -78.78 -79.47 Charged Nitrogen

ammonium -86.0 -87.89 -88.45 -87.20 -86.06 anilinium -66.0 -63.57 -63.38 -63.20 -63.43 pyridinium -59.0 -57.18 -57.18 -56.57 -55.66 methylammonium -71.0 -74.81 -74.77 -74.50 -74.24 nbutylammonium -66.0 -65.58 -65.67 -65.58 -65.06 N,N-dimethylanilinium -52.0 -50.98 -50.55 -51.51 -52.17 piperidinium -60.0 -56.34 -56.11 -56.27 -56.33 tbutylammonium -63.0 -61.58 -61.84 -61.84 -61.02 trimethylammonium -57.0 -59.02 -58.54 -59.14 -59.77

Charged Sulfur

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Table 5: Dataset - Validation I

Compound Exp PDAnum-1 PDAnum-2 PDAexp-1 PDAexp-2 Linear Alkanes

methane 2.00 1.15 1.15 1.30 1.30

pentane 2.30 2.05 2.05 2.24 2.23

Branched Alkanes

isobutane 2.30 1.78 1.78 1.95 1.94

Cycloalkanes

cyclopentane 1.20 1.78 1.78 1.88 1.87

Alkenes

ethylene 1.30 0.33 0.33 0.62 0.61

1-propene 1.30 0.71 0.71 0.89 0.87

Alkynes

1-pentyne 0.00 0.53 0.53 0.77 0.77

Arenes

naphtalene -2.40 -2.27 -2.27 -3.00 -2.89 phenanthrene -3.95 -3.07 -3.07 -4.14 -3.98

Alcohols

methanol -5.10 -7.55 -7.55 -5.79 -6.33 nbutanol -4.70 -5.74 -5.74 -4.42 -5.00 npropanol -4.80 -6.01 -6.01 -4.68 -5.26 Aldehydes

octanal -2.30 -2.29 -2.29 -2.49 -2.25

pentanal -3.00 -3.22 -3.22 -3.44 -3.18 Ketones

4-heptanone -2.90 -1.01 -1.01 -1.93 -1.92 acetophenone -4.60 -4.20 -4.20 -5.39 -5.20 Carboxylic Acids

hexanoic acid -6.20 -5.83 -5.83 -4.10 -3.14 Esters

methylbutanoate -2.80 -3.16 -3.16 -3.25 -2.83 methylpropanoate -2.90 -3.56 -3.56 -3.64 -3.20

Ethers

dimethylether -1.90 -2.94 -2.94 -2.77 -3.24 methylpropylether -1.70 -1.79 -1.79 -1.85 -2.35

Aliphatic amines

ethylamine -4.50 -4.76 -4.76 -3.57 -3.66 methylamine -4.60 -6.26 -6.26 -4.66 -4.78 piperidine -5.10 -1.53 -1.53 -2.67 -2.72 Aromatic amines

2-methylpyridine -4.80 -4.44 -4.44 -4.64 -4.44

aniline -4.90 -5.63 -4.73 -5.03 -8.47

Nitriles

butanonitrile -3.60 -4.41 -4.41 -3.28 -3.20 Amides

N,N-dimethylacetamide -8.50 -5.03 -5.03 -5.92 -5.90 Sulfurs

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Table 6: Dataset - Validation II

Compound Exp PDAnum-1 PDAnum-2 PDAexp-1 PDAexp-2 Multifunctionals

butenyne 0.00 -1.16 -1.16 -0.89 -0.87

m-hydroxybenzaldehyde -9.50 -10.87 -10.87 -10.14 -9.33 p-bromophenol -7.10 -7.63 -7.63 -6.20 -5.75

Halides

2-iodopropane -0.50 -1.10 -1.10 -0.78 -0.77 bromobenzene -1.50 -1.34 -1.34 -1.22 -1.12 chloroethane -0.60 -0.66 -0.66 -0.40 -0.39 chlorofluoromethane -0.80 -2.91 -2.91 -1.77 -1.62 dibromomethane -2.10 -1.29 -1.29 -0.74 -0.65 fluoromethane -0.20 -1.06 -1.06 -0.66 -0.65 tetrafluoromethane 3.20 -1.53 -1.53 1.022 1.33

Nitro

2-nitropropane -3.10 -1.82 -1.99 -1.46 -1.36 nitrobenzene -4.10 -3.17 -3.33 -2.90 -2.65 Charged Oxygen

benzoate -76.0 -71.47 -74.08 -74.11 -74.52 Charged Nitrogen

dimethylammonium -64.0 -65.52 -65.16 -65.46 -65.77 npropylammonium -67.0 -66.82 -66.92 -66.85 -66.34 tetramethylammonium -52.0 -54.64 -54.15 -54.91 -55.71

Charged sulfur

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2 II : Potentials of Mean Force of systems reported in table 8 and 9 of the

main article

3.5 4 4.5 5 5.5 6 6.5 7 7.5 8 8.5 9

C-C distance / Å

-1 -0.75 -0.5 -0.25 0 0.25 0.5 0.75 1

Free energy / kcal.mol

-1

Vacuum PDAnum-1 PDAexp-2 PDAexp-1

Figure 1: Potential of mean force Methane-Methane

4 4.5 5 5.5 6 6.5 7 7.5 8 8.5 9 9.5 10 10.5

center-center distance / Å

-2 -1.5 -1 -0.5 0 0.5 1 1.5 2

-1

Vacuum PDAnum-1 PDAexp-2 PDAexp-1

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5 6 7 8 9

-1

PDAnum-1 PDAnum-2 PDAexp-1 PDAexp-2

Figure 3: Potential of mean force Arg+ Arg+, planar

3 4 5 6 7 8 9 10

-1

Figure 4: Potential of mean force Arg+ Arg+, stacked

4 5 6 7 8 9

-1

PDAnum-1 PDAexp-1 PDAexp-2

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4 5 6 7 8 9

-1

Figure 6: Potential of mean force Glu- Glu-, planar

3 4 5 6 7

-1

Figure 7: Potential of mean force HisD Glu-, planar

3 4 5 6 7

-1

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3 4 5 6 7

-1

Figure 9: Potential of mean force HisP Glu-, planar

3 4 5 6 7

-1

Figure 10: Potential of mean force HisP HisE, planar

4 5 6 7 8 9

-1

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3 4 5 6 7 8

center-center distance / Å

-3 -2 -1 0 1 2

-1

Figure 12: Potential of mean force HisP HisP, stacked

3 4 5 6 7

N-C distance / Å

-4 -3 -2 -1 0 1 2

-1