title: Role of the Membrane Dipole Potential for Proton Transport in Gramicidin A Embedded in a DMPC Bilayer.
abstract: The membrane potential at the water/phospholipid interfaces may play a key role for proton conduction of gramicidin A (gA). Here we address this issue by Density Functional Theory-based molecular dynamics and metadynamics simulations. The calculations, performed on gA embedded in a solvated 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) model membrane environment (about 2,000 atoms), indicate that (i) the membrane dipole potential rises at the channel mouth by ∼0.4 V. A similar value has been measured for gA embedded in a DMPC monolayer; (ii) the calculated free energy barrier is located at the channel entrance, consistent with experiments comparing gA proton conduction in different bilayers. The electronic structures of the proton ligands (water molecules and peptide units) are similar to those in the bulk solvent. Based on these results, we suggest an important role of the membrane dipole potential for the free energy barrier of proton permeation of gA. This may provide a rationale for the large increase in the rate of proton conduction under application of a transmembrane voltage, as observed experimentally. Our calculations might suggest also a role for proton desolvation for the permeation process. This role has already emerged from EVB calculations on gA embedded in a model membrane.
authors.affiliation: Computational Biophysics, German Research School for Simulation Sciences, Joint venture of RWTH Aachen University and Forschungszentrum Jülich , Germany, D-52425 Jülich, Germany.|IAS-5, Computational Biomedicine, Institute for Advanced Simulation , Forschungszentrum Jülich, D-52425 Jülich, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Dreyer
authors.affiliation: Computational Biophysics, German Research School for Simulation Sciences, Joint venture of RWTH Aachen University and Forschungszentrum Jülich , Germany, D-52425 Jülich, Germany.|IAS-5, Computational Biomedicine, Institute for Advanced Simulation , Forschungszentrum Jülich, D-52425 Jülich, Germany.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Computational Biophysics, German Research School for Simulation Sciences, Joint venture of RWTH Aachen University and Forschungszentrum Jülich , Germany, D-52425 Jülich, Germany.|IAS-5, Computational Biomedicine, Institute for Advanced Simulation , Forschungszentrum Jülich, D-52425 Jülich, Germany.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Ippoliti
authors.affiliation: Computational Biophysics, German Research School for Simulation Sciences, Joint venture of RWTH Aachen University and Forschungszentrum Jülich , Germany, D-52425 Jülich, Germany.|IAS-5, Computational Biomedicine, Institute for Advanced Simulation , Forschungszentrum Jülich, D-52425 Jülich, Germany.
authors.forename: Paolo
authors.initials: P
authors.lastname: Carloni