Electrostatics of Deformable Lipid Membranes

Vorobyov, Igor; Bekker, Borislava; Allen, Toby W.

doi:10.1016/j.bpj.2010.03.046

Cited by 49 publications

(90 citation statements)

References 55 publications

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“…Additionally, our model suggests that ions that have moved into the bilayer do not sense the full strength of the membrane dipole potential because they remain in the head group region. This was also observed by Vorobyov and colleagues who used all-atom MD to show a similar result for MGuanH + permeation (Vorobyov et al 2010). …”

Section: Discussionsupporting

confidence: 80%

Continuum Approaches to Understanding Ion and Peptide Interactions with the Membrane

et al. 2014

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Experimental and computational studies have shown that cellular membranes deform to stabilize the inclusion of transmembrane (TM) proteins harboring charge. Recent analysis suggests that membrane bending helps to expose charged and polar residues to the aqueous environment and polar head groups. We previously used elasticity theory to identify membrane distortions that minimize the insertion of charged TM peptides into the membrane. Here, we extend our work by showing that it also provides a novel, computationally efficient method for exploring the energetics of ion and small peptide penetration into membranes. First, we show that the continuum method accurately reproduces energy profiles and membrane shapes generated from molecular simulations of bare ion permeation at a fraction of the computational cost. Next, we demonstrate that the dependence of the ion insertion energy on the membrane thickness arises primarily from the elastic properties of the membrane. Moreover, the continuum model readily provides a free energy decomposition into components not easily determined from molecular dynamics. Finally, we show that the energetics of membrane deformation strongly depend on membrane patch size both for ions and peptides. This dependence is particularly strong for peptides based on simulations of a known amphipathic, membrane binding peptide from the human pathogen Toxoplasma gondii. In total, we address shortcomings and advantages that arise from using a variety of computational methods in distinct biological contexts.

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Section: Discussionsupporting

confidence: 80%

Continuum Approaches to Understanding Ion and Peptide Interactions with the Membrane

et al. 2014

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“…The nonadditivity of multiple arginine translocation as a result of membrane deformation and water pore/defect formation has also been demonstrated by MacCallum et al 28 Our results exhibiting membrane structure perturbation support numerous earlier studies pointing to the importance of water defects on a local scale in facilitating structural and dynamic aspects of membrane biophysics. 66,68,69 …”

Section: Resultsmentioning

confidence: 99%

Free Energetics of Arginine Permeation into Model DMPC Lipid Bilayers: Coupling of Effective Counterion Concentration and Lateral Bilayer Dimensions

Patel

2013

J. Phys. Chem. B

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Mechanisms and underlying thermodynamic determinants of translocation of charged cationic peptides such as cell-penetrating peptides across the cellular membrane continue to receive much attention. Two widely-held views include endocytotic and non-endocytotic (diffusive) processes of permeant transfer across the bilayer. Considering a purely diffusive process, we consider the free energetics of translocation of a mono-arginine peptide mimic across a model DMPC bilayer. We compute potentials of mean force for the transfer of a charged mono-arginine peptide unit from water to the center of a 1,2-Dimyristoyl-sn-Glycero-3-Phosphocholine (DMPC) model lipid bilayer. We use fully atomistic molecular dynamics simulations coupled with the adaptive biasing force (ABF) method for free energy estimation. The estimated potential of mean force difference from bulk to bilayer center is 6.94 ± 0.28 kcal/mol. The order of magnitude of this prediction is consistent with past experimental estimates of arginine partitioning into physiological bilayers in the context of translocon-based experiments, though the correlation between the bench and computer experiments is not unambiguous. Moreover, the present value is roughly one-half of previous estimates based on all-atom molecular dynamics free energy calculations. We trace the differences between the present and earlier calculations to system sizes used in the simulations, and the dependence of the contributions to the free energy from various system components (water, lipids, ions, peptide) on overall system size. By varying the bilayer lateral dimensions in simulations using only sufficient numbers of counterions to maintain overall system charge neutrality, we find the possibility of an inherent convergent transfer free energy value.

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“…One further aspect is that the diversity of the NMR measurements and the experimental systems studied may contribute to obscuring of the underlying general principles. Here our aim is to bring together the available experimental NMR results into a comprehensive database that is transparent to all, ranging from NMR practitioners to non-specialists in the field of molecular simulations [9–16]. …”

Section: Membrane Lipids and Biomembranes Are Liquid-crystalline Mmentioning

confidence: 99%

An NMR database for simulations of membrane dynamics

Leftin

Brown

2011

Biochimica et Biophysica Acta (BBA) - Biomembranes

102

119

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Computational methods are powerful in capturing the results of experimental studies in terms of force fields that both explain and predict biological structures. Validation of molecular simulations requires comparison with experimental data to test and confirm computational predictions. Here we report a comprehensive database of NMR results for membrane phospholipids with interpretations intended to be accessible by non-NMR specialists. Experimental 13C–1H and 2H NMR segmental order parameters (SCH or SCD) and spin-lattice (Zeeman) relaxation times (T1Z) are summarized in convenient tabular form for various saturated, unsaturated, and biological membrane phospholipids. Segmental order parameters give direct information about bilayer structural properties, including the area per lipid and volumetric hydrocarbon thickness. In addition, relaxation rates provide complementary information about molecular dynamics. Particular attention is paid to the magnetic field dependence (frequency dispersion) of the NMR relaxation rates in terms of various simplified power laws. Model-free reduction of the T1Z studies in terms of a power-law formalism shows that the relaxation rates for saturated phosphatidylcholines follow a single frequency-dispersive trend within the MHz regime. We show how analytical models can guide the continued development of atomistic and coarse-grained force fields. Our interpretation suggests that lipid diffusion and collective order fluctuations are implicitly governed by the viscoelastic nature of the liquid-crystalline ensemble. Collective bilayer excitations are emergent over mesoscopic length scales that fall between the molecular and bilayer dimensions, and are important for lipid organization and lipid-protein interactions. Future conceptual advances and theoretical reductions will foster understanding of biomembrane structural dynamics through a synergy of NMR measurements and molecular simulations.

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Electrostatics of Deformable Lipid Membranes

Cited by 49 publications

References 55 publications

Continuum Approaches to Understanding Ion and Peptide Interactions with the Membrane

Continuum Approaches to Understanding Ion and Peptide Interactions with the Membrane

Free Energetics of Arginine Permeation into Model DMPC Lipid Bilayers: Coupling of Effective Counterion Concentration and Lateral Bilayer Dimensions

An NMR database for simulations of membrane dynamics

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