Figure 5. Unhinging pathway of FimH under tensile force in MD simulations.

(a) Location of the hinge axis (stereoview) determined with the program DynDom [61] by comparing the conformation of FimH at the end of the run pull 1 with its native conformation. (b) Sequence of rupture events of contacts between Ld and Pd versus distance from the hinge axis. A contact was defined as broken at the first time point when it ruptured and was not seen to reform within 300 ps. The Cα RMSD was calculated at the time of rupture (time averaged over 200 ps, Figures S3a, S4, S5a) in all six pulling runs and ranked according to a fractional ranking algorithm (where equal values receive the same raking as their respective ordinal rankings). The average and standard error of the mean of the ranked RMSD values are plotted against the distance of the respective contact from the hinge axis. The Cα RMSD from the native structure is a better measure of progress than the time of rupture itself, because rupture events are observed to occur in approximately the same order in every simulation but the time point when they occur varies across the simulations. The distance of a contact from the hinge axis is calculated as the distance of the geometric center of the involved side chains from the axis (in the case of hydrogen bonds, the geometric center of the D–H … A atoms is used). Significant inverse linear correlation (Pearson's ρ = 0.78; p value = 0.004) shows that the ranking number decreases with increasing distance, suggesting that the larger the distance from the hinge axis, the earlier the rupture of a contact.