Thermodynamic coupling between local lipid composition and ion channel conformation

It is well known that binding of specific lipids can modulate the response of voltage gated ion channels (VGICs) to the transmembrane potential. Less characterized is the effect of the membrane global phase behavior on the activity of VGICs. Here we explore the intriguing hypothesis that fluctuations in local lipid composition are coupled to the conformational transition resulting in conduction gating. To this end, we perform multi-microseconds coarse-grained molecular dynamics simulation of voltage-gated sodium channels in the resting and activated state.