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Then, the gating transition between resting and open conformation was investigated <jats:italic>in silico<\/jats:italic> by normal mode analysis using a physically meaningful description of protein flexibility. This analysis revealed a global quaternary twist motion that opens the ion pore. Second, it was found that most (24\/27) of the spontaneous mutations known to cause congenital myasthenia (and autosomal dominant nocturnal frontal lobe epilepsy) are located either at the interface between subunits or, within a given subunit, at the interface between rigid blocks. These interfaces are modified significantly by the twist mode together with significant changes of the tertiary organization of the subunits. 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