Model for the structure of the lipid bilayer.

Abstract

A detailed model for the structure and dynamics of the interior of the lipid bilayer in the liquid crystal phase is presented. The model includes two classes of motion: (i) the internal dynamics of the chains, determined from Brownian dynamics simulations with a continuous version of the Marcelja mean-field potential, and (ii) noncollective reorientation (axial rotation and wobble) of the entire molecule, introduced by a cone model. The basic unit of the model is a single lipid chain with field parameters adjusted to fit the 2H order parameters and the frequency-dependent 13C NMR T1 relaxation times of dipalmitoyl phosphatidylchollne bilayers. The chain configurations obtained from the trajectory are used to construct a representation of the bilayer. The resulting lipid assembly is consistent with NMR, neutron diffraction, surface area, and density data. It indicates that a high degree of chain disorder and entanglement exists in biological membranes.Lipid bilayers have two distinct phases in the physiological temperature range. The lower temperature Lp phase is highly ordered, with the hydrocarbon tails of the lipids primarily in the extended all-trans state (1, 2). At higher temperature, the bilayer enters the partially ordered liquid crystal (L,,) phase observed for biologically active membranes (1, 2). On going from Lp3 to La, the volume and fluidity of the bilayer increase, the thickness decreases, and the individual lipid undergoes a wide range of motions including: gauche-trans isomerizations, axial rotation, collective and noncollective tilting, out-of-plane deformations, and lateral diffusion (3)(4)(5)(6)(7)(8). The precise time scales, amplitudes, and degree of coupling of these motions remain uncertain both experimentally and theoretically. As a result, our knowledge of the underlying chain distribution is limited, and our understanding of the manner in which the bilayer adjusts to the presence of proteins and other membrane components (9) or to the high local curvature characteristic of membrane fusion (10) is incomplete.Much of the recent theoretical work on lipid structure has been based on either simplified approaches, such as the lattice (11) and mean-field (12-14) approximations, or on computationally intensive molecular dynamics (15, 16) and Monte Carlo (17) simulation methods. In lattice theories, the configurations for a system composed of a set of chain molecules, each consisting of connected segments, are generated on a lattice of specified symmetry. However, for large systems such as lipid bilayers, computer limitations require either a relatively coarse lattice or a short chain length. Consequently, the chains are idealized, and it is difficult to use the results of these calculations to interpret details of the real chain distributions. Very detailed descriptions of the bilayer come from molecular dynamics simulations with all-atom potentials (15). Unfortunately, many significant lipid motions are slow relative to the molecular dynamics subnanosecond time scale. The trans-gauche ...

An NMR database for simulations of membrane dynamics

“…In conjunction with experimental data provided by Brown et al (see Supplemental Material), rotational correlation times for the lipids were calculated using closed-form analytical formalisms (cf. Tables 4, 5, 6) [7,8,37] and were found to agree with experiment [9,78,169–171]. A current overview encompassing the current state of the art includes the membrane lipid simulations of Feller and Pastor [9], as well as atomistic simulations by Edholm et al [49], coarse-grain simulations by Marrink et al [12,48,172], and multi-scale dynamics simulations of Ayton and Voth [13,14,173].…”

Homology Modeling and Molecular Dynamics Simulations of the Mu Opioid Receptor in a Membrane–Aqueous System

“…[25,26,36] The conformers generated by the mean-field Monte-Carlo simulations, in so far as they agreed with the available experimental data, were representative of the phospholipid molecules found in a bilayer membrane in thermal equilibrium with its normal axis in the Z direction. In order to provide the primary hydration for the polar headgroup, approximately 20 water molecules around both the phosphate and the choline group were also included in the library; these water molecules were obtained from snapshot configurations during molecular-dynamics simulations of o-phosphorylcholine in bulk solution.…”

“…[23,24] The approach represents an extension of the work of Pastor and co-workers into the investigation of lipid bilayers. [25,26] In the setup of the membrane system, pre-equilibrated conformers for each phospholipid 1,2-dimiristoyl-SN-glycero-3-phosphorylcholine (DMPC) molecule were taken randomly from a set of 2000 that was previously generated from Monte Carlo simulations of an isolated DMPC molecule in the presence of a mean field. This molecule set was developed at 340 K, above the gel-liquid-crystal phase transition temperature.…”

Channel‐Type Molecular Structures. Part 2. Synthesis of Bouquet‐Shaped Molecules Based on a β‐Cyclodextrin Core

“…However, chain entangling may be detrimental to channel opening. Recent computational studies on lipid membranes led to the conclusion that lipid alkyl chains are significantly entangled [13]. Moreover, it is possible to draw the curve of the experimental NOEF us.…”