Fig. 4.

Binding mechanism of acetylcholine substrate on AChE. a Overlay of representative conformations along the binding pathway obtained from aMD simulations. Open conformations of the loop (defined by Cys69–Cys96 residues) and substrate conformations located outside the active site are represented in dark yellow (events 1–3), while closed conformations of the loop and substrate bound to the active site are shown in teal (events 4–6). Active site residues are shown in green. b Representation of the loop distance (in Å) between Pro78–Ser203 along the aMD simulation. Dark yellow solid line corresponds to open conformations of the loop, while teal color is used to highlight closed conformations. The open-to-closed transition of the loop is correlated to substrate binding, as shown by the purple solid line representing the distance (in Å) between the nitrogen atom of acetylcholine substrate and the oxygen atom of the side-chain of catalytic Ser203. Results are shown as the mean ± standard deviation (s.d.)