Strategies for Exploring Electrostatic and Nonelectrostatic Contributions to the Interaction of Helical Antimicrobial Peptides with Model Membranes

Alvares, Dayane S.; Cabrera, Marcia Perez dos Santos; Neto, João Ruggiero

doi:10.1016/bs.abl.2016.05.001

Cited by 7 publications

(3 citation statements)

References 167 publications

(228 reference statements)

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“…In experiment, the limit for PIP2 incorporation into bilayer vesicles with PC lipids is approximately 20%. , Cholesterol has a stabilizing effect on PIP2 vesicles, but this requires a minimum cholesterol fraction of 20 mol % . In contrast, monolayers can be formed with 100% PIP 2 . − Another example is phosphatidylethanolamine (PE), for which pure monolayers can be formed , but bilayers only exist in a narrow range of hydration . In fact, the large spontaneous curvature of PE promotes the inverse hexagonal (H II ) phase under more physiologically relevant conditions (in this case, full hydration) …”

Section: Discussion and Conclusionmentioning

confidence: 99%

Semi-automated Optimization of the CHARMM36 Lipid Force Field to Include Explicit Treatment of Long-Range Dispersion

Krämer

Venable

et al. 2021

J. Chem. Theory Comput.

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The development of the CHARMM lipid force field (FF) can be traced back to the early 1990s with its current version denoted CHARMM36 (C36). The parametrization of C36 utilized high-level quantum mechanical data and free energy calculations of model compounds before parameters were manually adjusted to yield agreement with experimental properties of lipid bilayers. While such manual fine-tuning of FF parameters is based on intuition and trial-and-error, automated methods can identify beneficial modifications of the parameters via their sensitivities and thereby guide the optimization process. This work introduces a semi-automated approach to reparametrize the CHARMM lipid FF with consistent inclusion of long-range dispersion through the Lennard-Jones particle-mesh Ewald (LJ-PME) approach. The optimization method is based on thermodynamic reweighting with regularization with respect to the C36 set. Two independent optimizations with different topology restrictions are presented. Targets of the optimizations are primarily liquid crystalline phase properties of lipid bilayers and the compression isotherm of monolayers. Pair correlation functions between water and lipid functional groups in aqueous solution are also included to address headgroup hydration. While the physics of the reweighting strategy itself is well-understood, applying it to heterogeneous, complex anisotropic systems poses additional challenges. These were overcome through careful selection of target properties and reweighting settings allowing for the successful incorporation of the explicit treatment of long-range dispersion, and we denote the newly optimized lipid force field as C36/LJ-PME. The current implementation of the optimization protocol will facilitate the future development of the CHARMM and related lipid force fields.

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Section: Discussion and Conclusionmentioning

confidence: 99%

Semi-automated Optimization of the CHARMM36 Lipid Force Field to Include Explicit Treatment of Long-Range Dispersion

Krämer

Venable

et al. 2021

J. Chem. Theory Comput.

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show abstract

“…86 In contrast, monolayers can be formed with 100% PIP2. [87][88][89] Another example is phosphatidylethanolamine (PE), for which pure monolayers can be formed 90,91 but bilayers only exist in a narrow range of hydration. 92 In fact, the large spontaneous curvature of PE promotes the inverse hexagonal (HII) phase under more physiologically relevant conditions (in this case, full hydration).…”

Section: Discussionmentioning

confidence: 99%

Semi-Automated Optimization of the CHARMM36 Lipid Force Field to Include Explicit Treatment of Long-Range Dispersion

Yu¹,

Krämer²,

Simmonett³

et al. 2020

Preprint

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The development of the CHARMM lipid force field (FF) can be traced back to the early 1990s with its current version denoted CHARMM36 (C36). The parametrization of C36 utilized high-level quantum mechanical data and free energy calculations of model compounds before parameters were manually adjusted to yield agreement with experimental properties of lipid bilayers. While such manual fine-tuning of FF parameters is based on intuition and trial-and-error, automated methods can identify beneficial modifications of the parameters via their sensitivities and thereby guide the optimization process. This paper introduces a semi-automated approach to reparametrize the CHARMM lipid FF with consistent inclusion of long-range dispersion through the LennardJones particle-mesh Ewald (LJ-PME) approach. The optimization method is based on thermodynamic reweighting with regularization with respect to the C36 set. Two independent optimizations with different topology restrictions are presented. Targets of the optimizations are primarily liquid crystalline phase properties of lipid bilayers and the compression isotherm of monolayers. Pair correlation functions between water and lipid functional groups in aqueous solution are also included to address headgroup hydration. While the physics of the reweighting strategy itself is well understood, applying it to heterogeneous, complex anisotropic systems poses additional challenges. These were overcome through careful selection of target properties and reweighting settings allowing for the successful incorporation of the explicit treatment of long-range dispersion, and we denote the newly optimized lipid force field as C36/LJ-PME. The current implementation of the optimization protocol will facilitate the future development of the CHARMM and related lipid force fields.<br>

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“…Adsorption of polycations and charged peptides on the surface of lipid membranes is a subject of various methods and their quantitative analysis is discussed in detail in a review [ 44 ]. A rich experimental material was obtained by the methods of fluorescence spectroscopy [ 45 , 46 , 47 ], atomic force microscopy [ 48 , 49 , 50 ], ellipsometry [ 43 , 51 ], by the technique of Langmuir monolayers [ 52 , 53 ], and by registration of the electrokinetic mobility in colloid suspensions [ 54 , 55 , 56 ].…”

Section: Electrostatic Contribution Of Polymers’ Interaction With Phospholipidsmentioning

confidence: 99%

Heterogeneity in Lateral Distribution of Polycations at the Surface of Lipid Membrane: From the Experimental Data to the Theoretical Model

2021

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Natural and synthetic polycations of different kinds attract substantial attention due to an increasing number of their applications in the biomedical industry and in pharmacology. The key characteristic determining the effectiveness of the majority of these applications is the number of macromolecules adsorbed on the surface of biological cells or their lipid models. Their study is complicated by a possible heterogeneity of polymer layer adsorbed on the membrane. Experimental methods reflecting the structure of the layer include the electrokinetic measurements in liposome suspension and the boundary potential of planar bilayer lipid membranes (BLM) and lipid monolayers with a mixed composition of lipids and the ionic media. In the review, we systematically analyze the methods of experimental registration and theoretical description of the laterally heterogeneous structures in the polymer layer published in the literature and in our previous studies. In particular, we consider a model based on classical theory of the electrical double layer, used to analyze the available data of the electrokinetic measurements in liposome suspension with polylysines of varying molecular mass. This model suggests a few parameters related to the heterogeneity of the polymer layer and allows determining the conditions for its appearance at the membrane surface. A further development of this theoretical approach is discussed.

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Strategies for Exploring Electrostatic and Nonelectrostatic Contributions to the Interaction of Helical Antimicrobial Peptides with Model Membranes

Cited by 7 publications

References 167 publications

Semi-automated Optimization of the CHARMM36 Lipid Force Field to Include Explicit Treatment of Long-Range Dispersion

Semi-automated Optimization of the CHARMM36 Lipid Force Field to Include Explicit Treatment of Long-Range Dispersion

Semi-Automated Optimization of the CHARMM36 Lipid Force Field to Include Explicit Treatment of Long-Range Dispersion

Heterogeneity in Lateral Distribution of Polycations at the Surface of Lipid Membrane: From the Experimental Data to the Theoretical Model

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