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Table 1 Experimental and calculated relative solvation free energies of side chain mimics [28]

From: QligFEP: an automated workflow for small molecule free energy calculations in Q

Sidechain mimic Exp Solvation free energies (∆∆G (kcal/mol)) X → CH4 λ0 ← λ0.5 → λ1
λ0 → λ1
X → Me Me → X Average Hysteresis
Propane − 0.05 0.20 ± 0.08 − 0.19 ± 0.19 0.20 0.01 0.08 ± 0.12
Isobutane − 0.34 − 0.27 ± 0.16 0.22 ± 0.09 − 0.25 0.05 − 0.04 ± 0.12
1-butane − 0.21 0.02 ± 0.25 − 0.33 ± 0.11 0.16 0.35 − 0.06 ± 0.11
Ethanol 6.82 7.05 ± 0.15 − 6.97 ± 0.11 7.01 0.08 6.75 ± 0.14
Methanol 7.00 6.69 ± 0.07 − 6.69 ± 0.07 6.69 0 6.62 ± 0.08
Methanethiol 3.18 2.01 ± 0.05 − 1.61 ± 0.09 1.81 0.4 1.78 ± 0.05
methylsulfanylethane 3.42 2.68 ± 0.08 − 2.39 ± 0.37 2.54 0.29 2.06 ± 0.11
Acetamide 11.62 10.91 ± 0.16 − 10.89 ± 0.08 10.90 0.02 10.93 ± 0.10
Propionamide 11.32 11.02 ± 0.31 − 11.09 ± 0.14 11.06 0.07 11.29 ± 0.15
Toluene 2.70 2.56 ± 0.48 − 1.96 ± 0.63 2.26 0.6 2.66 ± 0.35
p-cresol 8.05 8.16 ± 0.44 − 7.20 ± 0.12a 7.68a 0.96a 7.74 ± 0.48
4-methylimidaziole (NδH) 12.21b 9.86 ± 0.09 − 8.35 ± 0.96 9.11 1.51 10.22 ± 0.13
4-methylimidaziole (NεH) 12.21b 11.13 ± 0.15 − 10.85 ± 0.17 10.99 0.28 10.68 ± 0.34
3-methylindole 7.82 6.25 ± 0.37 − 5.25 ± 0.13a 5.75a 1.00a 7.41 ± 0.52
n-Propylguanidine (N2H3) 12.86 16.43 ± 0.44 − 15.47 ± 0.53 15.95 0.96 16.99 ± 0.29
Acetic acid (COOH) 8.64 8.16 ± 0.08 − 7.84 ± 0.09 8.00 0.32 8.07 ± 0.11
Propionic acid (COOH) 8.41 11.44 ± 0.17 − 11.41 ± 0.15 11.43 0.03 11.98 ± 0.23
butan-1-amine (NH2) 6.32 5.52 ± 0.22 − 4.37 ± 0.34 4.95 1.15 4.88 ± 0.38
n-Propylguanidine (N2H4+) 69.15 68.17 ± 0.51 − 67.05 ± 0.35 67.61 1.13 67.33 ± 0.71
Acetic acid (COO) 79.52 82.64 ± 0.10 − 82.21 ± 0.22 82.42 0.43 82.71 ± 0.07
Propionic acid (COO) 78.04 82.28 ± 0.21 − 82.63 ± 0.31 82.45 0.35 82.37 ± 0.13
butan-1-amine (NH3+) 73.07 77.71 ± 0.48 − 78.49 ± 0.16 78.10 0.78 78.39 ± 0.22
4-methylimidaziole (Nδ,εH2+) 64.23 67.75 ± 0.19 − 67.77 ± 0.18 67.75 0.02 67.42 ± 0.20
Statistical figures       
All sidechains R2 1.00 1.00 1.00   1.00
[95% CI] [0.99–1.00] [0.99–1.00] [0.99–1.00]   [0.99–1.00]
MAE 1.46 1.76 1.60   1.58
Slope 1.05 1.05 1.05   1.05
Intercept 0.43 0.89 0.66   0.43
Neutral sidechains R2 0.91 0.88 0.90   0.89
[95% CI] [0.77–0.97] [0.71− 0.96] [0.74− 0.96]   [0.74–0.96]
MAE 0.95 1.24 1.08   1.03
Slope 0.98 0.98 1.00   1.04
Intercept 0.21 0.43 0.32   0.36
Charged sidechains R2 0.92 0.86 0.89   0.89
[95% CI] [0.23–0.99] [0.07–0.99] [0.14–0.99]   [0.13–0.99]
MAE 3.33 3.67 3.48   3.57
Slope 1.11 1.31 1.12   1.16
Intercept 5.21 6.71 5.94   8.50
  1. aRelative free energies were calculated using sigmoidal sampling and λ = 101 windows
  2. bThe population distribution of a single proton NεH:NδH is approximately 80:20 [62]