Table 1.
Docking scores of current anticholinesterase drugs and marine metabolites into acetylcholinesterase receptors.
| Receptor | |||||
|---|---|---|---|---|---|
| Ligand | 1ACL | 1ACJ | 1DX6 | 1DX6 w/H2O | 1EVE |
| All Scores in kJ/mol | |||||
| Donepezil | −59.79 | −10.86 | −53.65 | −61.18 | −56.74 |
| Tacrine | −35.28 | −33.83 | −33.91 | −34.09 | −34.36 |
| Galanthamine | −35.28 | −35.77 | −36.47 | −38.76 | −36.38 |
| Acetylcholine | −31.78 | −34.06 | −31.99 | −31.25 | −31.61 |
| Onchidal | −47.51 | −44.28 | −48.55 | −47.37 | −46.14 |
| Marinoquinoline | −30.77 | −34.27 | −31.09 | −30.50 | −31.05 |
| Tetracyclopentazulene | −42.34 1 | −44.03 1 | −41.77 2 | −42.03 1 | −42.51 2 |
| Sargaquinoic acid | −67.92 | ND | −63.14 | −69.81 | −67.15 |
| Sargachromenol | −62.98 | −61.45 | −62.82 | −67.67 | −65.16 |
| Monooxofarnesylacetone | −59.00 | −55.34 | −57.81 | −50.22 | −57.36 |
| Dihydromonooxofarnesylacetone | −56.00 | −55.38 | −55.94 | −52.83 | −55.51 |
Docking galanthamine into its own receptor with and without this conserved water molecule both resulted in the crystallographic pose being selected. All inhibitors generated similar scores and poses in each receptor with the exception of donepezil in the 1ACJ receptor and onchidal. The best pose for onchidal was chosen. 1,2 Tetrazacyclopentazulene has two main poses (pose 1 scores are denoted by (1), pose 2 scores are denoted by (2)). ND Sargaquinoic acid would not dock into the 1ACJ receptor due to the Phe-330 ring position occluding the active site gorge (see Supplementary Figure S4).