ION-TRANSPORT IN THE GRAMICIDIN CHANNEL - FREE-ENERGY OF THE SOLVATED RIGHT-HANDED DIMER IN A MODEL MEMBRANE

The free energy profile of a Na+ ion along the axis of the gramicidin A dimer channel is calculated by molecular dynamics simulations. A cylindrical system is used that is based on a detailed atomic model of the gramicidin dimer, which is solvated at both ends of the channel and surrounded by a simplified model membrane. The entire system consists of 967 atoms and is treated with cylindrical periodic boundary conditions. The gramicidin channel was modeled from the right-handed head-to-head beta-helix dimer determined experimentally by two-dimensional NMR. Simulations were made to estimate the free energy profile in three regions: the transition from bulk-like solvation to single file, the single-file region at the entrance of the channel, and the intermonomer junction of the dimer channel. In each region, approximate corrections are introduced to account for hysteresis effects in the simulations. Binding sites are found at the extremities of the channel in agreement with experiment. The principal energy barrier is at the entrance of the channel in the single-rile region. No large activation energy barrier is introduced by the dehydration process, because the transformation from bulk to single-file solvation is progressive and takes place over a distance of 5-6 angstrom. The free energy simulation results obtained in this paper are joined with those calculated from a periodic model of the interior of the pore to construct an approximate free energy profile of the entire channel system.