Computational analysis of local membrane properties

In the field of biomolecular simulations, dynamics of phospholipid membranes is of special interest. A number of proteins, including channels, transporters, receptors and short peptides are embedded in lipid bilayers and tightly interact with phospholipids. While the experimental measurements report on the spatial and/or temporal average membrane properties, simulation results are not restricted to the average properties. In the current study, we present a collection of methods for an efficient local membrane property calculation, comprising bilayer thickness, area per lipid, deuterium order parameters, Gaussian and mean curvature. The local membrane property calculation allows for a direct mapping of the membrane features, which subsequently can be used for further analysis and visualization of the processes of interest. The main features of the described methods are highlighted in a number of membrane systems, namely: a pure dimyristoyl-phosphatidyl-choline (DMPC) bilayer, a fusion peptide interacting with a membrane, voltage-dependent anion channel protein embedded in a DMPC bilayer, cholesterol enriched bilayer and a coarse grained simulation of a curved palmitoyl-oleoyl-phosphatidyl-choline lipid membrane. The local membrane property analysis proves to provide an intuitive and detailed view on the observables that are otherwise interpreted as averaged bilayer properties.

[1]  Wataru Shinoda,et al.  A Voronoi analysis of lipid area fluctuation in a bilayer , 1998 .

[2]  Eric Jakobsson,et al.  Sphingomyelin-cholesterol domains in phospholipid membranes: atomistic simulation. , 2004, Biophysical journal.

[3]  Ilpo Vattulainen,et al.  Assessing the Nature of Lipid Raft Membranes , 2007, PLoS Comput. Biol..

[4]  Thomas Huber,et al.  G protein-coupled receptors self-assemble in dynamics simulations of model bilayers. , 2007, Journal of the American Chemical Society.

[5]  Herman J. C. Berendsen,et al.  MOLECULAR-DYNAMICS OF A BILAYER-MEMBRANE , 1983 .

[6]  Carlo H. Séquin,et al.  Robust geometric methods for surface modeling and manufacturing , 2004 .

[7]  Luca Monticelli,et al.  Free energy of WALP23 dimer association in DMPC, DPPC, and DOPC bilayers. , 2013, Chemistry and physics of lipids.

[8]  Yuji Sugita,et al.  Analysis of lipid surface area in protein–membrane systems combining voronoi tessellation and monte carlo integration methods , 2012, J. Comput. Chem..

[9]  Boris Martinac,et al.  Physical principles underlying the transduction of bilayer deformation forces during mechanosensitive channel gating , 2002, Nature Structural Biology.

[10]  Paul A. Wiggins,et al.  Emerging roles for lipids in shaping membrane-protein function , 2009, Nature.

[11]  O. Edholm,et al.  Areas of molecules in membranes consisting of mixtures. , 2005, Biophysical journal.

[12]  Carsten Kutzner,et al.  GROMACS 4:  Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation. , 2008, Journal of chemical theory and computation.

[13]  Oliver Beckstein,et al.  MDAnalysis: A toolkit for the analysis of molecular dynamics simulations , 2011, J. Comput. Chem..

[14]  E. Oldfield,et al.  Spectroscopic studies of specifically deuterium labeled membrane systems. Nuclear magnetic resonance investigation of the effects of cholesterol in model systems. , 1978, Biochemistry.

[15]  Peter Pohl,et al.  Design of peptide-membrane interactions to modulate single-file water transport through modified gramicidin channels. , 2012, Biophysical journal.

[16]  R. MacKinnon,et al.  Lipids in the structure, folding, and function of the KcsA K+ channel. , 2002, Biochemistry.

[17]  D. Marsh,et al.  Protein modulation of lipids, and vice-versa, in membranes. , 2008, Biochimica et biophysica acta.

[18]  D. Marsh,et al.  Activation of beef-heart cytochrome c oxidase by cardiolipin and analogues of cardiolipin. , 1990, Biochimica et biophysica acta.

[19]  E. Dufourc,et al.  On the relationship between C-C and C-D order parameters and its use for studying the conformation of lipid acyl chains in biomembranes , 1998 .

[20]  Matteo Frigo,et al.  A fast Fourier transform compiler , 1999, SIGP.

[21]  M. Parrinello,et al.  Canonical sampling through velocity rescaling. , 2007, The Journal of chemical physics.

[22]  E. Ikonen,et al.  Functional rafts in cell membranes , 1997, Nature.

[23]  T. Darden,et al.  A smooth particle mesh Ewald method , 1995 .

[24]  H. Berendsen,et al.  Interaction Models for Water in Relation to Protein Hydration , 1981 .

[25]  O. Berger,et al.  Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure, and constant temperature. , 1997, Biophysical journal.

[26]  Daniel L. Parton,et al.  Multi-scale simulation of the simian immunodeficiency virus fusion peptide. , 2012, The journal of physical chemistry. B.

[27]  Alan E. Mark,et al.  The GROMOS96 Manual and User Guide , 1996 .

[28]  J. Nagle,et al.  Structure of lipid bilayers. , 2000, Biochimica et biophysica acta.

[29]  Luís M. S. Loura,et al.  Molecular dynamics simulations of T-20 HIV fusion inhibitor interacting with model membranes. , 2011, Biophysical chemistry.

[30]  Yuguang Mu,et al.  Effects of cholesterol on pore formation in lipid bilayers induced by human islet amyloid polypeptide fragments: a coarse-grained molecular dynamics study. , 2011, Physical review. E, Statistical, nonlinear, and soft matter physics.

[31]  V. Shoshan-Barmatz,et al.  The voltage-dependent anion channel-1 modulates apoptotic cell death , 2005, Cell Death and Differentiation.

[32]  E. Oldfield,et al.  Molecular order and dynamics of phosphatidylcholine bilayer membranes in the presence of cholesterol, ergosterol and lanosterol: a comparative study using 2H-, 13C- and 31P-NMR spectroscopy. , 1995, Biochimica et biophysica acta.

[33]  A. J. Palace Carvalho,et al.  Molecular Dynamics Simulation of HIV Fusion Inhibitor T-1249: Insights on Peptide-Lipid Interaction , 2012, Comput. Math. Methods Medicine.

[34]  Ole G Mouritsen,et al.  Lipids do influence protein function-the hydrophobic matching hypothesis revisited. , 2004, Biochimica et biophysica acta.

[35]  W. Richards,et al.  Behavior of cholesterol and its effect on head group and chain conformations in lipid bilayers: a molecular dynamics study. , 1995, Biophysical journal.

[36]  A. Smondyrev,et al.  Structure of dipalmitoylphosphatidylcholine/cholesterol bilayer at low and high cholesterol concentrations: molecular dynamics simulation. , 1999, Biophysical journal.

[37]  John M. Lee.  Riemannian Manifolds: An Introduction to Curvature , 1997 .

[38]  T. E. Thompson,et al.  Modulation of phospholipid acyl chain order by cholesterol. A solid-state 2H nuclear magnetic resonance study. , 1990, Biochemistry.

[39]  Ilpo Vattulainen,et al.  Cationic DMPC/DMTAP lipid bilayers: molecular dynamics study. , 2003, Biophysical journal.

[40]  H. Grubmüller,et al.  Line-Tension Controlled Mechanism for Influenza Fusion , 2012, PloS one.

[41]  J. Seelig,et al.  Molecular order in cis and trans unsaturated phospholipid bilayers. , 1978, Biochemistry.

[42]  D. van der Spoel,et al.  Large influence of cholesterol on solute partitioning into lipid membranes. , 2012, Journal of the American Chemical Society.

[43]  A. Thomas,et al.  The N-terminal 12 residue long peptide of HIV gp41 is the minimal peptide sufficient to induce significant T-cell-like membrane destabilization in vitro. , 2006, Journal of molecular biology.

[44]  Peipei Ping,et al.  The crystal structure of mouse VDAC1 at 2.3 Å resolution reveals mechanistic insights into metabolite gating , 2008, Proceedings of the National Academy of Sciences.

[45]  J. D. de Pablo,et al.  Modulating membrane properties: the effect of trehalose and cholesterol on a phospholipid bilayer. , 2005, The journal of physical chemistry. B.

[46]  W. L. Jorgensen,et al.  Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids , 1996 .

[47]  Justin A. Lemkul,et al.  Perturbation of membranes by the amyloid β‐peptide – a molecular dynamics study , 2009, The FEBS journal.

[48]  E. Jakobsson,et al.  Cholesterol-induced modifications in lipid bilayers: a simulation study. , 2002, Biophysical journal.

[49]  H. Berendsen,et al.  Molecular dynamics simulation of a smectic liquid crystal with atomic detail , 1988 .

[50]  W. L. Jorgensen,et al.  Comparison of simple potential functions for simulating liquid water , 1983 .

[51]  B. Desbat,et al.  Structure and orientation study of fusion peptide FP23 of gp41 from HIV-1 alone or inserted into various lipid membrane models (mono-, bi- and multibi-layers) by FT-IR spectroscopies and Brewster angle microscopy. , 2005, Biochimica et biophysica acta.

[52]  A. Kukol,et al.  How the amyloid-β peptide and membranes affect each other: an extensive simulation study. , 2013, Biochimica et biophysica acta.

[53]  T. Darden,et al.  Particle mesh Ewald: An N⋅log(N) method for Ewald sums in large systems , 1993 .

[54]  Ilpo Vattulainen,et al.  Ordering effects of cholesterol and its analogues. , 2009, Biochimica et biophysica acta.

[55]  Siewert J. Marrink,et al.  The molecular face of lipid rafts in model membranes , 2008, Proceedings of the National Academy of Sciences.

[56]  R. Benz,et al.  Permeation of hydrophilic solutes through mitochondrial outer membranes: review on mitochondrial porins. , 1994, Biochimica et biophysica acta.

[57]  A. Saupe.  Kernresonanzen in kristallinen Flüssigkeiten und in kristallinflüssigen Lösungen. Teil I , 1964 .

[58]  William J. Allen,et al.  GridMAT‐MD: A grid‐based membrane analysis tool for use with molecular dynamics , 2009, J. Comput. Chem..

[59]  H. Berendsen,et al.  Molecular dynamics with coupling to an external bath , 1984 .

[60]  Erik G. Brandt,et al.  Determination of electron density profiles and area from simulations of undulating membranes. , 2011, Biophysical journal.

[61]  E. Lindahl,et al.  Molecular dynamics simulations of phospholipid bilayers with cholesterol. , 2003, Biophysical journal.

[62]  F. Reiss-Husson,et al.  Measurements of membrane thickness by small-angle scattering of suspensions: results for reconstituted Rhodopseudomonas sphaeroides reaction-center protein and for lipids , 1984 .

[63]  T. Róg,et al.  Non-polar interactions between cholesterol and phospholipids: a molecular dynamics simulation study. , 2003, Biophysical chemistry.

[64]  J. S. Hyde,et al.  Spin-label studies on phosphatidylcholine-cholesterol membranes: effects of alkyl chain length and unsaturation in the fluid phase. , 1986, Biochimica et biophysica acta.

[65]  J. Boggs,et al.  Effect of cholesterol and water on the rigidity and order of phosphatidylcholine bilayers. , 1972, Biochimica et biophysica acta.