Modulation of glycophorin A transmembrane helix interactions by lipid bilayers: molecular dynamics calculations

Petrache, Horia I.; Grossfield, Alan; MacKenzie, Kevin R.; Engelman, Donald M.; Woolf, Thomas B.

doi:10.1006/jmbi.2000.4072

Cited by 114 publications

(142 citation statements)

References 74 publications

(99 reference statements)

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“…By simulations on molecular detailed models it is instead possible to investigate how a protein may perturb the lipid bilayer, and at the same time undergo tilting. Indeed, MD simulations on atomistic models have confirmed too that, within the short time scale of these types of simulations, a protein can induce a deformation of the bilayer under mismatch conditions [219][220][221][222]; that the deformation is of the exponential type; and that its extent is protein-size dependent [223]. Also, by atomistic MD simulations it was found that membrane peptides may also tilt if embedded in a mismatched bilayer [224,225].…”

Section: Hydrophobic Mismatchmentioning

confidence: 98%

Mesoscopic models of biological membranes

Venturoli¹,

et al. 2006

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Phospholipids are the main components of biological membranes and dissolved in water these molecules self-assemble into closed structures, of which bilayers are the most relevant from a biological point of view. Lipid bilayers are often used, both in experimental and by theoretical investigations, as model systems to understand the fundamental properties of biomembranes. The properties of lipid bilayers can be studied at different time and length scales. For some properties it is sufficient to envision a membrane as an elastic sheet, while for others it is important to take into account the details of the individual atoms. In this review, we focus on an intermediate level, where groups of atoms are lumped into pseudo-particles to arrive at a coarse-grained, or mesoscopic, description of a bilayer, which is subsequently studied using molecular simulation.The aim of this review is to compare various strategies to coarse grain a biological membrane. The conclusion of this comparison is that there can be many valid different strategies, but that the results obtained by the various mesoscopic models are surprisingly consistent. A second objective of this review is to illustrate how mesoscopic models can be used to obtain a better understanding of experimental systems. The advantage of coarse-grained models is that these can be simulated very efficiently, so that phenomena involving large systems, or requiring a large number of simulations, can be studied in detail. This is illustrated with the study of the relation between the phase behavior of a membrane and the structure of the phospholipids, and the membrane structural changes due to molecules (such as alcohols, cholesterol and anesthetics) adsorbed to the membrane. We then discuss the effect of transmembrane peptides on the local structure of a membrane and the mechanism of vesicle fusion and fission.

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Section: Hydrophobic Mismatchmentioning

confidence: 98%

Mesoscopic models of biological membranes

Venturoli¹,

et al. 2006

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“…[165,166]), MD simulations have been extended to increasingly complex membrane proteins [167][168][169][170]. These simulations are able to provide insights into the nature of the interactions between membrane proteins and their lipid environment [168,[171][172][173][174] and analysis of those crystal structures of membrane proteins that contain lipids provides a detailed structural per-spective on lipid/protein interactions [56,175]. A number of experimental studies have also revealed the importance of bound lipid molecules for the stability and function of some membrane proteins [176][177][178][179][180] For example, in the case of the K + channel KcsA, acidic phospholipids appear to bind to specific (non-annular) sites at which they play a role in refolding and possibly in function [181][182][183].…”

Section: Protein/lipid Interactionsmentioning

confidence: 99%

Molecular dynamics simulations of potassium channels

Domene

2007

Open Chemistry

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Despite the complexity of ion-channels, MD simulations based on realistic all-atom models have become a powerful technique for providing accurate descriptions of the structure and dynamics of these systems, complementing and reinforcing experimental work. Successful multidisciplinary collaborations, progress in the experimental determination of three-dimensional structures of membrane proteins together with new algorithms for molecular simulations and the increasing speed and availability of supercomputers, have made possible a considerable progress in this area of biophysics. This review aims at highlighting some of the work in the area of potassium channels and molecular dynamics simulations where numerous fundamental questions about the structure, function, folding and dynamics of these systems remain as yet unresolved challenges.

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“…18,19 With the structure of the GpA dimer solved, molecular modeling has revealed that close residue contacts, required for an overall attractive van der Waals interaction, were allowed by the small, compliant Gly residues at the helical interface. [20][21][22] It is now believed that, in general, the highly conserved GxxxG motif 4 allows the close packing of transmembrane helices in other proteins to occur.…”

Section: Introductionmentioning

confidence: 99%

Environmental Effects on Glycophorin A Folding and Structure Examined through Molecular Simulations

Nanda

Sachs

Petrache

et al. 2005

J. Chem. Theory Comput.

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Abstract:The human erythrocyte sialoglycoprotein glycophorin A (GpA) has been used extensively in experiment and simulations as a model of transmembrane helix-dimer formation, emphasizing the critical role of specific residue-residue interactions between helices in dimer stability. While the tertiary dimer structure is modulated by the hydrophobic lipid bilayer environment, we show that interactions of GpA with ordered interfacial water are commensurate to intrahelical forces. The role of lipid-water interface in stabilizing transmembrane proteins is not yet understood; however, dramatic water reordering in the presence of the transmembrane domains is observed from simulations and is possibly measurable by experiment. Interfacial interactions including anisotropic interactions with the polar headgroups might favor parallel association of transmembrane helices. To quantify forces capable of disrupting the GpA dimer, we generate folding/unfolding intermediates by replacement of the lipid bilayer with water, eliminating not only the native hydrophobic environment but also the native interfacial water region. Dramatic changes in the secondary, helical structures occur, with a transition from i,i+4 R-helix to i,i+5 π-helix and concomitant perturbation of the tertiary structure. Enforcing the native R-helix secondary structure by soft dihedral restraints restores the native tertiary structure, in essence substituting for the lack of the lipid-water interface. We suggest that differentiation between interactions within the lipid bilayer, including interactions with lipid headgroups and interfacial water can enrich our understanding of the thermodynamic stability of transmembrane domains.

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Modulation of glycophorin A transmembrane helix interactions by lipid bilayers: molecular dynamics calculations

Cited by 114 publications

References 74 publications

Mesoscopic models of biological membranes

Mesoscopic models of biological membranes

Molecular dynamics simulations of potassium channels

Environmental Effects on Glycophorin A Folding and Structure Examined through Molecular Simulations

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