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. Author manuscript; available in PMC: 2011 Aug 26.
Published in final edited form as: J Phys Chem B. 2010 Aug 26;114(33):10889–10896. doi: 10.1021/jp104989b

Table 1.

The FEP-calculated free energy changes (in kcal/mol) in comparison with the experimental kinetic data for (−)-cocaine hydrolysis catalyzed by BChE mutants.

Mutation ΔGEa ΔGTS1a ΔΔG(1→2)
A199S/A328W/Y332G → A199S/F227A/A328W/Y332G 6.12 (0.29) 4.98 (0.25) −1.13
A199S/A328W/Y332G → A199S/S287A/A328W/Y332G 8.58 (0.16) 7.78 (0.50) −0.80
A199S/S287A/A328W/Y332G → A199S/S287G/A328W/Y332G −5.67 (0.54) −5.82 (0.52) −0.15
A199S/S287G/A328W/Y332G → A199S/F227A/S287G/A328W/Y332G 6.85 (0.44) 5.80 (0.51) −1.05
A199S/A328W/Y332G → A199S/S287G/A328W/Y332Gb 2.91 1.96 −0.95
A199S/A328W/Y332G → A199S/F227A/S287G/A328W/Y332Gc 9.76 7.76 −2.00
a

ΔGE and ΔGTS1 are the mutation-caused free energy changes for the free enzyme and transition state, respectively. The number in the parenthesis after the ΔGE or ΔGTS1 value refers to the root-mean-square fluctuation (RMSF) of the ΔGE or ΔGTS1 values calculated starting from the five initial structures. The corresponding standard error (SE) can be estimated from the RMSF value by using Eq. (8) and N = 5, i.e. SE = RMSF/2.236.

b

The theoretical results were derived from the FEP results obtained for the enzyme changes A199S/A328W/Y332G → A199S/S287A/A328W/Y332G → A199S/S287G/A328W/Y332G.

c

The theoretical results were derived from the FEP results obtained for the enzyme changes A199S/A328W/Y332G → A199S/S287A/A328W/Y332G → A199S/S287G/A328W/Y332G → A199S/F227A/S287G/A328W/Y332G.