Temperature Dependence of Gramicidin Channel Transport and Structure

Abstract

The gramicidin dipeptide is a small, cation-selective ion channel. Recent experiments have indicated that gramicidin can conduct ions at elevated temperatures. Since gramicidin is an efficient proton conductor, it is possible that this channel may have applications in fuel cell technology. In this study, we examine the temperature dependence of gramicidin A channel transport and structure with molecular dynamics simulations. In particular, the potentials of mean force (PMFs) for potassium ion motion through the channel are computed at five temperatures in the range 300−360 K. The channel displays a decrease in the free energy barrier height as the temperature increases. In addition, the enthalpic and entropic components of the free energy are computed, indicating a substantial enthalpy−entropy compensation and a positive entropy change when the ion enters the channel. The positive entropy change results from a reduction in fluctuations of ion interaction energies in the pore relative to those in the bulk solvent. The overall dimeric channel structure is maintained at 360 K for time scales up to 100 ns. In addition, higher temperatures affect the distributions of hydrogen bonds at the dimer interface, conformations of the N-terminal domain that may block the pore, channel bending angles, and distances between dimers. These findings may be related to the gating of the channel, although no complete dimer dissociation events were observed in the simulations.

Polarizable force field development for lipids and their efficient applications in membrane proteins

“…In the case of K + , two outer and inner cation‐binding sites are observed near the pore entrance at | z | = 12 Å and | z | = 9 Å, respectively. The positions of the cation‐binding sites observed in AMOEBA are consistent with the experimental observation and previously calculated results . In the case of Na + , the deeper binding site is observed in | z | = 9 Å.…”

“…The single channel conductance is overestimated by several orders of magnitude compared to the experiment observation, depending on the additive force field and MD simulation protocol used. For example, previous calculated PMF for K + permeation using the additive force field demonstrated an unexpectedly high free energy barrier of 10−20 kcal/mol, whereas the experimental data indicated that the K + permeates through the gA channel with a small free energy barrier . On the other hand, Sandeep and co‐workers used the charge equilibration polarizable force field to evaluate the PMF for K + permeation in the gA channel within a small 20 DMPC bilayer …”

“…The positions of the cation-binding sites observed in AMOEBA are consistent with the experimental observation 124 and previously calculated results. 115,127,128 In the case of Na + , the deeper binding site is observed in |z| = 9 Å.…”

Propeller-shaped molecules with a thiazole hub: structural landscape and hydrazone cap mediated tunable host behavior in 4-hydrazino-1,3-thiazoles

“…One dimensional (1D) water chains/water wires and the design of their synthetic hosts attract enormous research interest owing to their key roles in fundamental biological processes [36][37][38][39] exemplified by the selective transport of water across cells in protein aquaporins, [40][41][42][43][44][45] and the transport of protons in Gramicidin A membrane channels, [46][47][48][49][50] cytochrome oxidase, [51][52][53][54][55][56] and bacteriorhodopsin. [57][58][59] The probable role of water in protein folding 60,61 and the correlation of water pathways to the activation of G-coupled receptors 62 all point towards the topical interest in water channels.…”

A Polarizable Atomic Multipole-Based Force Field for Molecular Dynamics Simulations of Anionic Lipids

“…The free energy profiles of K + and Na + permeating through the gramicidin A channel embedded in DMPC are characterized by our group with using the AMOEBA polarizable force field by our group [ 36 ]. The previous calculated potential mean forces (PMF) for K + permeation using the additive force field demonstrated an unexpectedly high free energy barrier of 10–20 kcal/mol [ 18 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ], whereas the experimental data indicated that the K + permeates through the gA channel with a small free energy barrier [ 49 , 50 ]. Compared with the results produced by additive force field, the free energy barriers for K + /Na + through gA channel are significantly decreased [ 36 ], which are depended on the explicitly described polarization effects in AMOEBA.…”