36. Conformational flexibility of cyclic imine phycotoxins revealed by long-timescale molecular dynamics simulations

Abstract

Macrocyclic spiroimine phycotoxins constitute a growing class of structurally related marine neurotoxins contaminating shellfish (Molgo et al., 2014). Most of them are strong antagonists of nicotinic acetylcholine receptors (nAChRs), and a few ones showed moderate activities against muscarinic acetylcholine receptors (mAChRs). During recent years this field has witnessed important developments with regard to chemical synthesis, X-ray crystallography, electrophysiology, detection methods and molecular modelling. In this study, the conformational flexibility of representative cyclic imine phycotoxins (gymnodimines, spirolides, pinnatoxins, pteriatoxins, spiro-prorocentrimine and prorocentrolides) was evaluated using long-timescale all-atom molecular dynamics simulations in OPLS-AA force field.