Ligand-AChE complexes, structures

As compared to the natural ligand ACh, the conformation of anatoxin is relatively rigid, with only one rotatable bond as compared to four in ACh. This simplifies the ability to correlate the structural conformation of the ligand to efficacy, and, consequently, attention has been directed toward determining the active conformation through the use of sterically constrained analogs of the s-ds and s-trans conformers of anatoxin-a [19,40-44]). Although current evidence leans toward s-trans as the active conformation, condusive evidence, such as a crystal structure of (+)-anatoxin-a in complex with an nACh receptor, is still needed. 

The initial solution of the crystal structure of the Torpedo enzyme [28], followed by the mammalian AChE structure [29], revealed that the active center serine lies at the base of a rather narrow gorge that is lined heavily with aromatic residues (Fig. 11-6). The enzyme carries a net negative charge, and an electrostatic dipole is oriented on the enzyme to facilitate diffusional entry of cationic ligands. Crystal structures of several inhibitors in a complex with AChE also have been elucidated [25]. 

As in the previous example, the known crystal structures of Ach E-inhibitor complexes were taken as positive control to test the usability of AutoDock. The same standard docking parameters were taken as for the analysis of the ER ligands [12]. Due to the flexibility and the few polar functional groups of the inhi-... 

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