Gap junctions provide a communication pathway between adjacent cells. They are formed by paired connexons that reside in the plasma membrane of their respective cell and their activity can be modulated by the bilayer composition. In this work, we study the dynamic behavior of a Cx26 connexon embedded in a POPC lipid bilayer, studying: the membrane protein interactions and the ion flux though the connexon pore. We analyzed extensive atomistic molecular dynamics simulations for different conditions, with and without calcium ions. We found that lipid-protein interactions were mainly mediated by hydrogen bonds. Specific amino acids were identified forming hydrogen bonds with the POPC lipids (ARG98, ARG127, ARG165, ARG216, LYS22, LYS221, LYS223, LYS224, SER19, SER131, SER162, SER219, SER222, THR18 and TYR97, TYR155, TYR212, and TYR217). In the presence of calcium ions, we found subtle differences on the HB lifetimes. Finally, these MD simulations are able to identify and explain differential chlorine flux through the pore depending on the presence or absence of the calcium ions and its distribution within the pore.
Keywords: APBS; Connexon; Cx26 hemichannel; Molecular dynamics; POPC.