Lipids in channel pore: potential gating mechanism or simulation artifact?

Abstract

Coarse-grained (CG) Martini force field in molecular dynamics simulations is currently the most popular model to study protein-lipid interactions for large protein size and long-timescale. Literature has reported lipids entering the ion channel pore during CG simulation, such as in mechanosensitive Piezo1 channel1, however, no experimental evidence addressed whether these lipids should be in the pore. Moreover, our previous 7.9µs simulation of a reduced Piezo1 all-atom simulation did not show permanent pore occlusion by lipids in the nonconducting state.