How SNARE molecules mediate membrane fusion: Recent insights from molecular simulations

► Molecular simulations have revisited the original stalk-pore hypothesis. ► Initial membrane merger is determined by the free energy of leaflet approach. ► SNARE complexes reduce the free energy of leaflet approach and are actively involved in the lipidic transition states. ► SNARE complexes release mechanical stress to actively overcome the barrier against stalk expansion and enforce opening of the fusion pore. ► SNARE complexes can prevent the formation/expansion of a metastable hemifusion diaphragm.