1,596 research outputs found
Dynamic Implicit-Solvent Coarse-Grained Models of Lipid Bilayer Membranes : Fluctuating Hydrodynamics Thermostat
Many coarse-grained models have been developed for equilibrium studies of
lipid bilayer membranes. To achieve in simulations access to length-scales and
time-scales difficult to attain in fully atomistic molecular dynamics, these
coarse-grained models provide a reduced description of the molecular degrees of
freedom and often remove entirely representation of the solvent degrees of
freedom. In such implicit-solvent models the solvent contributions are treated
through effective interaction terms within an effective potential for the free
energy. For investigations of kinetics, Langevin dynamics is often used.
However, for many dynamical processes within bilayers this approach is
insufficient since it neglects important correlations and dynamical
contributions that are missing as a result of the momentum transfer that would
have occurred through the solvent. To address this issue, we introduce a new
thermostat based on fluctuating hydrodynamics for dynamic simulations of
implicit-solvent coarse-grained models. Our approach couples the coarse-grained
degrees of freedom to a stochastic continuum field that accounts for both the
solvent hydrodynamics and thermal fluctuations. We show our approach captures
important correlations in the dynamics of lipid bilayers that are missing in
simulations performed using conventional Langevin dynamics. For both planar
bilayer sheets and bilayer vesicles, we investigate the diffusivity of lipids,
spatial correlations, and lipid flow within the bilayer. The presented
fluctuating hydrodynamics approaches provide a promising way to extend
implicit-solvent coarse-grained lipid models for use in studies of dynamical
processes within bilayers
Computational studies of biomembrane systems: Theoretical considerations, simulation models, and applications
This chapter summarizes several approaches combining theory, simulation and
experiment that aim for a better understanding of phenomena in lipid bilayers
and membrane protein systems, covering topics such as lipid rafts, membrane
mediated interactions, attraction between transmembrane proteins, and
aggregation in biomembranes leading to large superstructures such as the light
harvesting complex of green plants. After a general overview of theoretical
considerations and continuum theory of lipid membranes we introduce different
options for simulations of biomembrane systems, addressing questions such as:
What can be learned from generic models? When is it expedient to go beyond
them? And what are the merits and challenges for systematic coarse graining and
quasi-atomistic coarse grained models that ensure a certain chemical
specificity
Coarse-grained simulation of transmembrane peptides in the gel phase
We use Dissipative Particle Dynamics simulations, combined with parallel tempering and umbrella sampling, to investigate the potential of mean force between model transmembrane peptides in the various phases of a lipid bilayer, including the low-temperature gel phase.
The observed oscillations in the effective interaction between peptides are consistent with the different structures of the surrounding lipid phases
The order-disorder transition in model lipid bilayers is a first-order hexatic to liquid phase transition
We characterize the order-disorder transition in a model lipid bilayer using
molecular dynamics simulations. We find that the ordered phase is hexatic. In
particular, in-plane structures possess a finite concentration of 5-7
disclination pairs that diffuse throughout the plane of the bilayer, and
further, in-plane structures exhibit long-range orientational order and
short-range translational order. In contrast, the disordered phase is liquid.
The transition between the two phases is first order. Specifically, it exhibits
hysteresis, and coexistence exhibits an interface with capillary scaling. The
location of the interface and its spatial fluctuations are analyzed with a
spatial field constructed from a rotational-invariant for local 6-fold
orientational order. As a result of finite interfacial tension, there
necessarily exist associated forces of assembly between membrane-bound solutes
that pre-melt the ordered phase.Comment: Addressed the comments from colleagues, corrected typos, clarified
text, updated references. The new draft also contains new results relating to
the hexatic phas
Coarse-grained simulation of amphiphilic self-assembly
We present a computer simulation study of amphiphilic self assembly performed using a computationally efficient single-site model based on Gay-Berne and Lennard-Jones particles. Molecular dynamics simulations of these systems show that free self-assembly of micellar, bilayer and inverse micelle arrangements can be readily achieved for a single model parameterisation. This self-assembly is predominantly driven by the anisotropy of the amphiphile-solvent interaction, amphiphile-amphiphile interactions being found to be of secondary importance. While amphiphile concentration is the main determinant of phase stability, molecular parameters such as headgroup size and interaction strength also have measurable affects on system properties. </p
Carbohydrate-derived amphiphilic macromolecules: a biophysical structural characterization and analysis of binding behaviors to model membranes.
The design and synthesis of enhanced membrane-intercalating biomaterials for drug delivery or vascular membrane targeting is currently challenged by the lack of screening and prediction tools. The present work demonstrates the generation of a Quantitative Structural Activity Relationship model (QSAR) to make a priori predictions. Amphiphilic macromolecules (AMs) "stealth lipids" built on aldaric and uronic acids frameworks attached to poly(ethylene glycol) (PEG) polymer tails were developed to form self-assembling micelles. In the present study, a defined set of novel AM structures were investigated in terms of their binding to lipid membrane bilayers using Quartz Crystal Microbalance with Dissipation (QCM-D) experiments coupled with computational coarse-grained molecular dynamics (CG MD) and all-atom MD (AA MD) simulations. The CG MD simulations capture the insertion dynamics of the AM lipophilic backbones into the lipid bilayer with the PEGylated tail directed into bulk water. QCM-D measurements with Voigt viscoelastic model analysis enabled the quantitation of the mass gain and rate of interaction between the AM and the lipid bilayer surface. Thus, this study yielded insights about variations in the functional activity of AM materials with minute compositional or stereochemical differences based on membrane binding, which has translational potential for transplanting these materials in vivo. More broadly, it demonstrates an integrated computational-experimental approach, which can offer a promising strategy for the in silico design and screening of therapeutic candidate materials
General model of phospholipid bilayers in fluid phase within the single chain mean field theory
Coarse-grained model for saturated (DCPC, DLPC, DMPC, DPPC, DSPC) and
unsaturated (POPC, DOPC) phospholipids is introduced within the Single Chain
Mean Field theory. A single set of parameters adjusted for DMPC bilayers gives
an adequate description of equilibrium and mechanical properties of a range of
saturated lipid molecules that differ only in length of their hydrophobic tails
and unsaturated (POPC, DOPC) phospholipids which have double bonds in the
tails. A double bond is modeled with a fixed angle of 120 degrees, while the
rest of the parameters are kept the same as saturated lipids. The thickness of
the bilayer and its hydrophobic core, the compressibility and the equilibrium
area per lipid correspond to experimentally measured values for each lipid,
changing linearly with the length of the tail. The model for unsaturated
phospholipids also fetches main thermodynamical properties of the bilayers.
This model is used for an accurate estimation of the free energies of the
compressed or stretched bilayers in stacks or multilayers and gives reasonable
estimates for free energies. The proposed model may further be used for studies
of mixtures of lipids, small molecule inclusions, interactions of bilayers with
embedded proteins
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