Simulation of lipid bilayer self-assembly using all-atom lipid force fields

Skjevik, Åge A.; Madej, Benjamin D.; Dickson, Callum J.; Lin, Charles; Teigen, Knut; Walker, Ross C.; Gould, Ian R.

doi:10.1039/c5cp07379k

Cited by 43 publications

(49 citation statements)

References 68 publications

(158 reference statements)

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“…Several combinations of the simulation parameters were tested in order to establish the optimum settings. It was found, as previously described 34 , that an initial simulation using an isotropic pressure scheme, followed by an adequately long semi-isotropic coupling, yielded the best results. In order to favor the membrane formation during the isotropic coupling stage, it was found that the initial cubic simulation box side length has to be commensurate with the side length of the membrane patch, which is expected to be finally formed.…”

Section: Exploratory Self Aggregation Simulations Of the Shc8 Systemsupporting

confidence: 61%

Water permeation across artificial I-quartet membrane channels: from structure to disorder

et al. 2018

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Artificial water channels (AWCs) have been designed for water transport across membranes with the aim to mimic the high water permeability observed for biological systems such as aquaporins (∼108-109 water molecules per s per channel), as well as their selectivity to reject ion permeation at the same time. Recent works on designed self-assembling alkylureido-ethylimidazole compounds forming imidazole-quartet channels (I-quartets), have shown both high water permeability and total ionic-rejection. I-quartets are thus promising candidates for further development of AWCs. However, the molecular mechanism of water permeation as well as I-quartet organization and stability in a membrane environment need to be fully understood to guide their optimal design. Here, we use a wide range of all-atom molecular dynamics (MD) simulations and their analysis to understand the structure/activity relationships of the I-quartet channels. Four different types with varying alkyl chain length or chirality have been studied in a complex fully hydrated lipid bilayer environment at both microsecond and nanosecond scale. Microsecond simulations show two distinct behaviors; (i) two out of four systems maintain chiral dipolar oriented water wires, but also undergo a strong reorganization of the crystal shape, (ii) the two other I-quartet channels completely lose the initial organization, nonetheless keeping a water transport activity. Short MD simulations with higher time resolution were conducted to characterize the dynamic properties of water molecules in these model channels and provided a detailed hypothesis on the molecular mechanism of water permeation. The ordered confined water was characterized with quantitative measures of hydrogen-bond life-time and single particle dynamics, showing variability among I-quartet channels. We will further discuss the underlying assumptions, currently based on self-aggregation simulations and crystal patches embedded in lipid bilayer simulations and attempt to describe possible alternative approaches to computationally capture the water permeation mechanism and the self-assembly process of these AWCs.

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Section: Exploratory Self Aggregation Simulations Of the Shc8 Systemsupporting

confidence: 61%

Water permeation across artificial I-quartet membrane channels: from structure to disorder

et al. 2018

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“…To be useful, force fields must strike the correct balance between the various intermolecular interactions: biomolecule-water, biomolecule-biomolecule, water-water, water-ion, ion-counterion and ion-biomolecule interactions; in this last case, the main contribution would come from the interaction between the ions in solution and the charged sites of the biomolecules. Classical, fixed-charge force fields for biomolecules in water have been under evolution for decades and are now quite successful at predicting binding affinities 6 and the folded structure of small proteins, 7-9 the self-assembly of phospholipid bilayers, 10 the importance of electrostatics in DNA, and DNA-protein interactions. 11,12 These force fields were parameterized against experimental observables that reflect the balance between ionwater, biomolecule-water and water-water interactions (e.g., free energies of hydration).…”

Section: Introductionmentioning

confidence: 99%

Developing force fields when experimental data is sparse: AMBER/GAFF-compatible parameters for inorganic and alkyl oxoanions

Kashefolgheta

Verde

2017

Phys. Chem. Chem. Phys.

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We present a set of Lennard-Jones parameters for classical, all-atom models of acetate and various alkylated and non-alkylated forms of sulfate, sulfonate and phosphate ions, optimized to reproduce their interactions with water and with the physiologically relevant sodium, ammonium and methylammonium cations. The parameters are internally consistent and are fully compatible with the Generalized Amber Force Field (GAFF), the AMBER force field for proteins, the accompanying TIP3P water model and the sodium model of Joung and Cheatham. The parameters were developed primarily relying on experimental information -hydration free energies and solution activity derivatives at 0.5 m concentration -with ab initio, gas phase calculations being used for the cases where experimental information is missing. The ab initio parameterization scheme presented here is distinct from other approaches because it explicitly connects gas phase binding energies to intermolecular interactions in solution. We demonstrate that the original GAFF/AMBER parameters often overestimate anion-cation interactions, leading to an excessive number of contact ion pairs in solutions of carboxylate ions, and to aggregation in solutions of divalent ions. GAFF/AMBER parameters lead to excessive numbers of salt bridges in proteins and of contact ion pairs between sodium and acidic protein groups, issues that are resolved by using the optimized parameters presented here.

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“…For example, Skjevik et al demonstrated that a self-assembled phospholipid structure forms a spontaneous stable lamellar bilayer in few microseconds in an aqueous environment with a clear preferential orientation with polar head groups pointing outside [ 15 ]. However—experimentally—the bilayer packing is related to full water hydration (Van der Waals interactions) through hydrogen bridges [ 14 , 16 , 17 , 18 , 19 ] and lipid interactions [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Thermal Response Analysis of Phospholipid Bilayers Using Ellipsometric Techniques

et al. 2017

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Biomimetic planar artificial membranes have been widely studied due to their multiple applications in several research fields. Their humectation and thermal response are crucial for reaching stability; these characteristics are related to the molecular organization inside the bilayer, which is affected by the aliphatic chain length, saturations, and molecule polarity, among others. Bilayer stability becomes a fundamental factor when technological devices are developed—like biosensors—based on those systems. Thermal studies were performed for different types of phosphatidylcholine (PC) molecules: two pure PC bilayers and four binary PC mixtures. These analyses were carried out through the detection of slight changes in their optical and structural parameters via Ellipsometry and Surface Plasmon Resonance (SPR) techniques. Phospholipid bilayers were prepared by Langmuir-Blodgett technique and deposited over a hydrophilic silicon wafer. Their molecular inclination degree, mobility, and stability of the different phases were detected and analyzed through bilayer thickness changes and their optical phase-amplitude response. Results show that certain binary lipid mixtures—with differences in its aliphatic chain length—present a co-existence of two thermal responses due to non-ideal mixing.

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Simulation of lipid bilayer self-assembly using all-atom lipid force fields

Cited by 43 publications

References 68 publications

Water permeation across artificial I-quartet membrane channels: from structure to disorder

Water permeation across artificial I-quartet membrane channels: from structure to disorder

Developing force fields when experimental data is sparse: AMBER/GAFF-compatible parameters for inorganic and alkyl oxoanions

Thermal Response Analysis of Phospholipid Bilayers Using Ellipsometric Techniques

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