Molecular dynamics simulation lipid bilayers

Solute transport and partitioning in lipid bilayers molecular dynamics simulations... 

Key words Lipid bilayer - molecular dynamics simulations - computer simulation - permeability - transport... 

Since the random-coil model is a good model of bulk n-alkane, it is not so surprising that the present model is successful in reproducing a wide range of the static properties of the lipid bilayer molecular dynamics simulation. 

T. R. Stouch and D. Bassolino. Movement of small molecules in lipid bilayers Molecular dynamics simulation studies. In K. M. Merz and B. Roux (eds.). Biological Membranes. A Molecular Perspective from Computation and Experiment, pages 255-278. Birkhauser, Boston, 1996. 

The examination of peptide membrane interactions requires characterisation of the position, orientation, structure and dynamics of the peptide in the lipid bilayer as well as its effects on surrounding lipids. While molecular dynamics simulation can in principle furnish complete structural and dynamical information, considerable obstacles exist to obtaining accurate results, due partly to inexact force fields and other approximations in simulation methodology, and... 

Water-membrane interfaces are discussed separately in this volume (see Environment of a Membrane Protein Molecular Dynamics Studies of Lipid Bilayers and Permeation of Lipid Membranes Molecular Dynamics Simulations). 

Molecular Dynamics DNA Molecular Dynamics Simulations of Nucleic Acids Molecular Dynamics Studies of Lipid Bilayers Molecular Dynamics Techniques and Applications to Proteins. 

A second series of papers was published by Stouch and co-workers. Bassolino-Klimas et al. calculated diffusion coefficients for benzene molecules in a DMPC bilayer as function of their location in the bilayer. In later papers this work was extended to study the effect of different temperatures on the preferred locations of benzene molecules and the effect of solute size, studying a drug analog. Simulations of permeation and diffusion through and in bilayers will be described more elaborately in Permeation of Lipid Membranes Molecular Dynamics Simulations. 

Intermolecular Interactions by Perturbation Theory Molecular Dynamics and Hybrid Monte Carlo in Systems with Multiple Time Scales and Long-range Forces Reference System Propagator Algorithms Molecular Dynamics Simulations of Nucleic Acids Molecular Dynamics Studies of Lipid Bilayers Molecular Dynamics Techniques and Applications to Proteins Monte Carlo Simulations for Liquid Monte Carlo Simulations for Polymers. 

The first molecular dynamics simulations of a lipid bilayer which used an explicit representation of all the molecules was performed by van der Ploeg and Berendsen in 1982 [van dei Ploeg and Berendsen 1982]. Their simulation contained 32 decanoate molecules arranged in two layers of sixteen molecules each. Periodic boundary conditions were employed and a xmited atom force potential was used to model the interactions. The head groups were restrained using a harmonic potential of the form ... 

This chapter has given an overview of the structure and dynamics of lipid and water molecules in membrane systems, viewed with atomic resolution by molecular dynamics simulations of fully hydrated phospholipid bilayers. The calculations have permitted a detailed picture of the solvation of the lipid polar groups to be developed, and this picture has been used to elucidate the molecular origins of the dipole potential. The solvation structure has been discussed in terms of a somewhat arbitrary, but useful, definition of bound and bulk water molecules. 

Studies of the effect of permeant s size on the translational diffusion in membranes suggest that a free-volume model is appropriate for the description of diffusion processes in the bilayers [93]. The dynamic motion of the chains of the membrane lipids and proteins may result in the formation of transient pockets of free volume or cavities into which a permeant molecule can enter. Diffusion occurs when a permeant jumps from a donor to an acceptor cavity. Results from recent molecular dynamics simulations suggest that the free volume transport mechanism is more likely to be operative in the core of the bilayer [84]. In the more ordered region of the bilayer, a kink shift diffusion mechanism is more likely to occur [84,94]. Kinks may be pictured as dynamic structural defects representing small, mobile free volumes in the hydrocarbon phase of the membrane, i.e., conformational kink g tg ) isomers of the hydrocarbon chains resulting from thermal motion [52] (Fig. 8). Small molecules can enter the small free volumes of the kinks and migrate across the membrane together with the kinks. 

Gumbart, J. Wang, Y. Aksimentiev, A. Tajkhorshid, E. Schulten, K., Molecular dynamics simulations of proteins in lipid bilayers, Curr. Opin. Struct. Biol. Aug 2005,15, 423—A3. ... 

Figure 1 (Plate 1). A molecular view of a small section of a flat lipid bilayer generated by molecular dynamics simulations. The bilayers are composed of l-stearoyl-2-docosa-hexaenoyl-5M-g]ycero-3-phosphatidylcholine lipids, i.e. the sn 1 chain is 18 C atoms long and the sn2 chain has 22 carbons, including six cis double bonds. The hydrophobic core is in the centre of the picture, and the hydrated head-group regions are both on top and bottom of the view graph. The head group is zwitterionic and no salt has been added. From [102], Reproduced by permission of the American Physical Society. Copyright (2003)...

The strong point of molecular dynamic simulations is that, for the particular model, the results are (nearly) exact. In particular, the simulations take all necessary excluded-volume correlations into account. However, still it is not advisable to have blind confidence in the predictions of MD. The simulations typically treat the system classically, many parameters that together define the force field are subject to fine-tuning, and one always should be cautious about the statistical certainty. In passing, we will touch upon some more limitations when we discuss more details of MD simulation of lipid systems. We will not go into all the details here, because the use of MD simulation to study the lipid bilayer has recently been reviewed by other authors already [31,32]. Our idea is to present sufficient information to allow a critical evaluation of the method, and to set the stage for comparison with alternative approaches. 

Lindahl, E. and Edholm, O. (2000). Spatial and energetic-entropic decomposition of surface tension in lipid bilayers from molecular dynamics simulations, J. Chem. Phys., 113, 3882-3893. 

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. 

Hyvonen, M. T., Rantala, T. T. and Ala-Korpela, M. (1997). Structure and dynamic properties of diunsaturated l-palmitoyl-2-linoleoyl-,sM-glycero-3-phosphatidylcholine lipid bilayer from molecular dynamics simulation, Biophys. J., 73, 2907-2923. 

Chiu, S. W., Clark, M., Balaji, V., Subramaniam, S., Scott, H. L. and Jakobsson, E. (1995). Incorporation of surface tension into molecular dynamics simulation of an interface a fluid phase lipid bilayer membrane, Biophys. J., 69,1230-1245. 

Leermakers, F. A. M., Rabinovich, A. L. and Balabaev, N. K. (2003). Self-consistent field modeling of hydrated unsaturated lipid bilayers in the liquid-crystal phase and comparison to molecular dynamics simulations, Phys. Rev. E, 67, 011910. 

Xiang, T. X. and Anderson, B. D. (1999). Molecular dissolution processes in lipid bilayers a molecular dynamics simulation, J. Chem. Phys., 110, 1807-1818. 

Bassolino-Klimas, D., Alper, H. E. and Stouch, T. R. (1993). Solute diffusion in lipid bilayer membranes an atomic level study by molecular dynamics simulation,... 

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