Study of the interaction of Huperzia saururus Lycopodium alkaloids with the acetylcholinesterase enzyme

MARCELO PUIATTI; BORIONI JOSE; M. G. VALLEJO; CABRERA J.L; AGNESE M; M. G. ORTEGA; PIERINI, ADRIANA

JOURNAL OF MOLECULAR GRAPHICS & MODELLING.

ELSEVIER SCIENCE INC

Año: 2013 vol. 44 p. 136 - 144

1093-3263

tIn the present study, we describe and compare the binding modes of three Lycopodium alkaloids(sauroine, 6-hydroxylycopodine and sauroxine; isolated from Huperzia saururus) and huperzine A withthe enzyme acetylcholinesterase. Refinement and rescoring of the docking poses (obtained with differentprograms) with an all atom force field helped to improve the quality of the protein?ligand complexes.Molecular dynamics simulations were performed to investigate the complexes and the alkaloid?s bind-ing modes. The combination of the latter two methodologies indicated that binding in the active site isfavored for the active compounds. On the other hand, similar binding energies in both the active and theperipheral sites were obtained for sauroine, thus explaining its experimentally determined lack of activ-ity. MM-GBSA predicted the order of binding energies in agreement with the experimental IC50values.