Figure 1

(a) Correlation between the differences in experimental inhibitor ln(k _on ) and differences in electrostatic potentials of AchE and (b). leave-two-out cross-validation for prediction of k _on values for the inhibitor TFK+ and AChE. Each point in part (a) represents a pair of AChE variants for which the natural log (ln) of the difference in association rate constant, k_on, for the inhibitor TFK+ is plotted on the x-axis and the average electrostatic potential difference in the comparison region is plotted on the y-axis. The straight line corresponds to the best linear fit and is given by y = -1.39*x. The data are for wild-type AChE and 10 mutants (see Table 1, no k_onvalue for TFK+ is available for mutant 04). For leave-two-out cross-validation predictions presented in (b), 2 cases were omitted when deriving the correlation factor α in formula (1) and these 2 cases were predicted using formula (1) with the derived factor α. Predictions are shown as vertical lines connecting minimum and maximum values from all (55) different predictions.