Lipid bilayers ensembles

Venable, R. M., Brooks, B. R. and Pastor, R. W. (2000). Molecular dynamics simulations of gel phase lipid bilayers in constant pressure and constant surface area ensembles, J. Chem. Phys., 112, 4822-4832. 

This review emphasizes an intriguing and potentially useful aspect of the polymerization of lipid assemblies, i.e. polymerization and domain formation within an ensemble of molecules that is usually composed of more than one amphiphile. General aspects of domain formation in binary lipid mixtures and the polymerization of lipid bilayers are discussed in Sects. 1.1 and 1.2, respectively. More detailed reviews of these topics are available as noted. The mutual interactions of lipid domains and lipid polymerization are described in the subsequent sections. Given the proper circumstances the polymerization of lipid monolayers or bilayers can lock in the phase separation of lipids, i.e. pre-existing lipid domains within the ensemble as described in Sect. 2. Section 3 reviews the evidence for the polymerization-initiated phase separation of polymeric domains from the unpolymerized lipids. 

As discussed above, the photosynthetic reaction center solves the problem of rapid charge recombination by spatially separating the electron and hole across the lipid bilayer. In order to achieve photoinitiated electron transfer across this large distance, the reaction center uses a multistep sequence of electron transfers through an ensemble of donor and acceptor moieties. The same strategy may be successfully employed in photosynthesis models, and has been since 1983 [42-45]. The basic idea may be illustrated by reference to a triad Dj-D2-A, where D2 represents a pigment whose excited state will act as an electron donor, Di is a secondary donor, and A is an electron acceptor. Excitation of D2 will lead to the following potential electron transfer events. 

Allen and Bevan (80) have applied the SMD technique to the study of reversible inhibitors of monoamine oxidase B, and this paper will be used as an example for discussion of the constant velocity SMD pulling method. They used the Gromacs suite of biomolecular simulation programs (18) with the united-atom Gromos 43al force field to parameterize the lipid bilayer, protein, and small-molecule inhibitors. The protein was inserted into their mixed bilayer composed of phosphatidyl choline (POPC) and phosphatidyl ethanolamine (POPE) lipids in a ratio known to be consistent for a mitochondrial membrane. Each inhibitor-bound system studied was preequilibrated in a periodic box of SPC water (20) with the simulations run using the NPT ensemble at 300 K and 1 atm pressure for 20 ns. Full atomic coordinates and velocities were saved in 200-ps increments giving five replicates for each inhibitor-bound system. A dummy atom was attached to an atom (the SMD atom shown in Fig. 7) of the inhibitor nearest to the... 

It should be further mentioned that the choice of the ensemble also depends on whether or not the solvent is explicitly modeled. In particular, care has to be exerted concerning the number of intensive variables of the ensemble. This can be understood considering the Gibbs phase rule for interfaces [93] f = 2 + c - p, with / being the number of independent intensive variables needed to describe the interface, p the number of different phases in the interface, and c denoting the number of different components. A lipid bilayer comprising one sort of lipid embedded into an implicit solvent corresponds to a one-component system c = 1, in one-phase state so that p = 1 hence / = 2. On the other hand, a model with explicit solvent yields c = 2, p = 1, and / = 3. Thus, implicit solvent models can be simulated within nXT ensemble while for explicit-solvent models an additional intensive quantity has to be controlled, e.g., the nPzzXT ensemble is appropriate. 

In a related paper, Ikeda et al. has presented a combined use of replica-exchange MD and solid-state MAS NMR spectral simulations for determining the structure and orientation of membrane-bound peptide." First, an ensemble of low energy structures of mastoparan-X, a wasp venom peptide, in lipid bilayers was generated by replica exchange molecular dynamics (REMD) simulation with the implicit membrane/solvent model. Next, peptide structures compatible with experimental chemical shifts of C,, Cp and C carbons were selected from the ensemble. Chemical shifts of C, alone were sufficient for the selection with backbone rmsd s of 0.8 A from the experimentally determined structure. The dipolar couplings between the peptide protons and lipid nuclei were obtained from the C-... 

Vosegaard and coworkers study lipid bilayer dynamics and calculate P solid-state NMR spectra from ensembles generated in extended MD simulations providing more comprehensive information than traditional NMR dynamical models. They have included the antimicrobial peptide... 

NH tautomeric compounds for probing the structure and dynamics of organized ensembles, such as lipid bilayers and micelles. 

Another parameter that can have a great influence on the results obtained is the type of the simulation performed. Generally, simulations are carried out at constant particle number (N). The volume (V) and energy (E) of the simulated system can be held constant, leading to a so-called NVE, or microcanonical, ensemble. When the volume and temperature are held constant, this yields a canonical or NVT ensemble. In both cases, the size of the simulated system is chosen in such a way as to represent the desired state of the phospholipid, mostly the liquid crystalline La phase. The surface per lipid and the thickness of the bilayer are set based on experimental values and remain unchanged during the simulation. Therefore, the system is not able to adjust its size and thickness. 

The structure-function relations of glycolipids in lipid membranes has been reviewed. This is a challenging endeavour which has mainly been faced through NMR spectroscopy and computational modelling, using model membranes such as micelles, bicelles, and bilayers. Glycolipid structure is rarely, if ever, a unique low-energy conformer, but an ensemble of dynamic states. ... 

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