MOLECULAR-DYNAMICS SIMULATION OF THE GRAMICIDIN CHANNEL IN A PHOSPHOLIPID-BILAYER

A molecular dynamics simulation of the gramicidin A channel in an expl icit dimyristoyl phosphatidylcholine bilayer was generated to study th e details of lipid-protein interactions at the microscopic level. Soli d state NMR properties of the channel averaged over the 500-psec traje ctory are in excellent agreement with available experimental data. In contrast with the assumptions of macroscopic models, the membrane/solu tion interface region is found to be at least 12 Angstrom thick. The t ryptophan side chains, located within the interface, are found to form hydrogen bonds with the ester carbonyl groups of the lipids and with water, suggesting their important contribution to the stability of mem brane proteins. Individual lipid-protein interactions are seen to vary from near 0 to -50 kcal/mol. The most strongly interacting conformati ons are short-lived and have a nearly equal contribution from both van der Waals and electrostatic energies. This approach for performing mo lecular dynamics simulations of membrane pro teins in explicit phospho lipid bilayers should help in studying the structure, dynamics, and en ergetics of lipid-protein interactions.