Proton Transfer in Gramicidin Water Wires in Phospholipid Bilayers: Attenuation by Phosphoethanolamine

Chernyshev, Anatoly; Cukierman, Samuel

doi:10.1529/biophysj.106.083352

Cited by 17 publications

(49 citation statements)

References 45 publications

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“…The proton flux obtained by these simulations agrees with experimental values. [23][24][25][26] Energy Profile of the Proton Channel. In order to analyze the proton transfer process within the channel, it is instructive to calculate first the energy profile along the proton transfer path.…”

Section: Resultsmentioning

confidence: 99%

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Simulating the Proton Transfer in Gramicidin A by a Sequential Dynamical Monte Carlo Method

et al. 2008

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The large interest in long-range proton transfer in biomolecules is triggered by its importance for many biochemical processes such as biological energy transduction and drug detoxification. Since long-range proton transfer occurs on a microsecond time scale, simulating this process on a molecular level is still a challenging task and not possible with standard simulation methods. In general, the dynamics of a reactive system can be described by a master equation. A natural way to describe long-range charge transfer in biomolecules is to decompose the process into elementary steps which are transitions between microstates. Each microstate has a defined protonation pattern. Although such a master equation can in principle be solved analytically, it is often too demanding to solve this equation because of the large number of microstates. In this paper, we describe a new method which solves the master equation by a sequential dynamical Monte Carlo algorithm. Starting from one microstate, the evolution of the system is simulated as a stochastic process. The energetic parameters required for these simulations are determined by continuum electrostatic calculations. We apply this method to simulate the proton transfer through gramicidin A, a transmembrane proton channel, in dependence on the applied membrane potential and the pH value of the solution. As elementary steps in our reaction, we consider proton uptake and release, proton transfer along a hydrogen bond, and rotations of water molecules that constitute a proton wire through the channel. A simulation of 8 mus length took about 5 min on an Intel Pentium 4 CPU with 3.2 GHz. We obtained good agreement with experimental data for the proton flux through gramicidin A over a wide range of pH values and membrane potentials. We find that proton desolvation as well as water rotations are equally important for the proton transfer through gramicidin A at physiological membrane potentials. Our method allows to simulate long-range charge transfer in biological systems at time scales, which are not accessible by other methods.

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Section: Resultsmentioning

confidence: 99%

“…This proton transfer across the membrane was measured experimentally in dependence on the pH value and the membrane potential. [23][24][25][26] In this article, we describe a new DMC algorithm to simulate charge transfer in biomolecules. We discuss the theoretical background and the implementation of the method.…”

Section: Introductionmentioning

confidence: 99%

Simulating the Proton Transfer in Gramicidin A by a Sequential Dynamical Monte Carlo Method

et al. 2008

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“…It appears to select small monovalent cations, bind bivalent cations, while reject anions. Because of its simplicity in structure and wide visibility in literature [13, 15, 25], we utilize it as the membrane channel to study the proton transport. In our approach, the GA structure is downloaded from the PDB, and the pdb file is processed by the PDB2PQR [21], in which the radii and partial charges are adopted from the CHARMM force field values [30].…”

Section: Numerical Simulationsmentioning

confidence: 99%

“…There are other experimental data on proton conductance available [1,13,18] but under different experimental conditions. First, the experimental data provided by Cukierman et al [18] offer proton conductions recorded with natural Gramicidin A and with its Dioxolane-Linked dimer in different lipid bi-layers (phosphatidylethanolamine-phosphatidylcholine, or PEPC and glycerymonooleate, or GMO).…”

Section: Numerical Simulationsmentioning

confidence: 99%

“…Their experimental studies were carried out for low (9.8 mM) and high (1578 mM) proton concentrations against the transmembrane voltages. Additionally, in another piece of work [13], the attenuation of proton transfer in Gramicidin water wires by phosphoethanolamine was investigated and a number of I-V curves were provided. It is impossible to fit all the experimental data by a single group of parameters because of the difference in experimental conditions and lipid membrane types.…”

Section: Numerical Simulationsmentioning

confidence: 99%

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Quantum Dynamics in Continuum for Proton Transport I: Basic Formulation

Chen

Guo²

2013

Commun. comput. phys.

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Proton transport is one of the most important and interesting phenomena in living cells. The present work proposes a multiscale/multiphysics model for the understanding of the molecular mechanism of proton transport in transmembrane proteins. We describe proton dynamics quantum mechanically via a density functional approach while implicitly model other solvent ions as a dielectric continuum to reduce the number of degrees of freedom. The densities of all other ions in the solvent are assumed to obey the Boltzmann distribution. The impact of protein molecular structure and its charge polarization on the proton transport is considered explicitly at the atomic level. We formulate a total free energy functional to put proton kinetic and potential energies as well as electrostatic energy of all ions on an equal footing. The variational principle is employed to derive nonlinear governing equations for the proton transport system. Generalized Poisson-Boltzmann equation and Kohn-Sham equation are obtained from the variational framework. Theoretical formulations for the proton density and proton conductance are constructed based on fundamental principles. The molecular surface of the channel protein is utilized to split the discrete protein domain and the continuum solvent domain, and facilitate the multiscale discrete/continuum/quantum descriptions. A number of mathematical algorithms, including the Dirichlet to Neumann mapping, matched interface and boundary method, Gummel iteration, and Krylov space techniques are utilized to implement the proposed model in a computationally efficient manner. The Gramicidin A (GA) channel is used to demonstrate the performance of the proposed proton transport model and validate the efficiency of proposed mathematical algorithms. The electrostatic characteristics of the GA channel is analyzed with a wide range of model parameters. The proton conductances are studied over a number of applied voltages and reference concentrations. A comparison with experimental data verifies the present model predictions and validates the proposed model.

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Quantum dynamics in continuum for proton transport II: Variational solvent–solute interface

Chen

Guo

2011

Numer Methods Biomed Eng

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Proton transport plays an important role in biological energy transduction and sensory systems. Therefore it has attracted much attention in biological science and biomedical engineering in the past few decades. The present work proposes a multiscale/multiphysics model for the understanding of the molecular mechanism of proton transport in transmembrane proteins involving continuum, atomic and quantum descriptions, assisted with the evolution, formation and visualization of membrane channel surfaces. We describe proton dynamics quantum mechanically via a new density functional theory based on the Boltzmann statistics, while implicitly model numerous solvent molecules as a dielectric continuum to reduce the number of degrees of freedom. The density of all other ions in the solvent is assumed to obey the Boltzmann distribution in a dynamic manner. The impact of protein molecular structure and its charge polarization on the proton transport is considered explicitly at the atomic scale. A variational solute-solvent interface is designed to separate the explicit molecule and implicit solvent regions. We formulate a total free energy functional to put proton kinetic and potential energies, the free energy of all other ions, the polar and nonpolar energies of the whole system on an equal footing. The variational principle is employed to derive coupled governing equations for the proton transport system. Generalized Laplace-Beltrami equation, generalized Poisson-Boltzmann equation and generalized Kohn-Sham equation are obtained from the present variational framework. The variational solvent-solute interface is generated and visualized to facilitate the multiscale discrete/continuum/quantum descriptions. Theoretical formulations for the proton density and conductance are constructed based on fundamental laws of physics. A number of mathematical algorithms, including the Dirichlet to Neumann mapping (DNM), matched interface and boundary (MIB) method, Gummel iteration, and Krylov space techniques are utilized to implement the proposed model in a computationally efficient manner. The Gramicidin A (GA) channel is used to validate the performance of the proposed proton transport model and demonstrate the efficiency of the proposed mathematical algorithms. The proton channel conductances are studied over a number of applied voltages and reference concentrations. A comparison with experimental data verifies the present model predictions and confirms the proposed model.

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Proton Transfer in Gramicidin Water Wires in Phospholipid Bilayers: Attenuation by Phosphoethanolamine

Cited by 17 publications

References 45 publications

Simulating the Proton Transfer in Gramicidin A by a Sequential Dynamical Monte Carlo Method

Simulating the Proton Transfer in Gramicidin A by a Sequential Dynamical Monte Carlo Method

Quantum Dynamics in Continuum for Proton Transport I: Basic Formulation

Quantum dynamics in continuum for proton transport II: Variational solvent–solute interface

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