Lipids molecular dynamics

Permeation process of small molecules across lipid membranes studied by molecular dynamics simulations. J. Phys. Chem. 100 (1996) 16729-16738. 

Marrink, S.J., Jahnig, F., Berendsen, H.J.C. Proton transport across transient single-file water pores in a lipid membrane studied by molecular dynamics simulations. Biophys. J. 71 (1996) 632-647. 

M2irrink et al., 1998] Marrink, S.-J., Berger, O., Tieleman, R, and Jahnig, F. Adhesion forces of lipids in a phospholipid membrane studied by molecular dynamics dimulations. Biophys. J. 74 (1998) 931-943... 

Stepaniants et al., 1997] Stepaniants, S., Izrailev, S., and Schulten, K. Extraction of lipids from phospholipid membranes by steered molecular dynamics. J. Mol. Model. 3 (1997) 473-475... 

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 ... 

Has D ], K Tu and M L Klein 1997. Atomic-scale Molecular Dynamics Simulations of Lipid Membranes. Current Opinion in Colloid and Interfaee Seienee 2 15-26. 

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. 

W Pfeiffer, T Henkel, E Sackmann, W Knoll, D Richter. Europhys Lett 8 201-206, 1989. RW Pastor, SE Eeller. Time scales of lipid dynamics and molecular dynamics. In KM Merz Jr, B Roux, eds. Biological Membranes A Molecular Perspective from Computation and Experiment. Boston Birkhauser, 1996, pp 3-30. 

VMD is designed for the visualization and analysis of biological systems such as proteins, nucleic acids, and lipid bilayer assemblies. It may be used to view more general molecules, as VMD can read several different structural file formats and display the contained structure. VMD provides a wide variety of methods for rendering and coloring a molecule. VMD can be used to animate and analyze the trajectory of a molecular dynamics (MD) simulation. 

A review is given of the application of Molecular Dynamics (MD) computer simulation to complex molecular systems. Three topics are treated in particular the computation of free energy from simulations, applied to the prediction of the binding constant of an inhibitor to the enzyme dihydrofolate reductase the use of MD simulations in structural refinements based on two-dimensional high-resolution nuclear magnetic resonance data, applied to the lac repressor headpiece the simulation of a hydrated lipid bilayer in atomic detail. The latter shows a rather diffuse structure of the hydrophilic head group layer with considerable local compensation of charge density. 

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. 

Demchenko AP, Yesylevskyy SO (2009) Nanoscopic description of biomembrane electrostatics results of molecular dynamics simulations and fluorescence probing. Chem Phys Lipids 160(2) 63-84... 

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. ... 

Tieleman, D. P., Marrink, S. J., and Berendsen, H. J. C., A computer perspective of membranes molecular dynamics studies of lipid bilayer systems, Biochim. Biophys. Acta., 1997, 3333, 235-270. 

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 strategy in a molecular dynamics simulation is conceptually fairly simple. The first step is to consider a set of molecules. Then it is necessary to choose initial positions of all atoms, such that they do not physically overlap, and that all bonds between the atoms have a reasonable length. Subsequently, it is necessary to specify the initial velocities of all the atoms. The velocities must preferably be consistent with the temperature in the system. Finally, and most importantly, it is necessary to define the force-field parameters. In effect the force field defines the potential energy of each atom. This value is a complicated sum of many contributions that can be computed when the distances of a given atom to all other atoms in the system are known. In the simulation, the spatial evolution as well as the velocity evolution of all molecules is found by solving the classical Newton equations of mechanics. The basic outcome of the simulation comprises the coordinates and velocities of all atoms as a function of the time. Thus, structural information, such as lipid conformations or membrane thickness, is readily available. Thermodynamic information is more expensive to obtain, but in principle this can be extracted from a long simulation trajectory. 

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. 

In principle, MC algorithms can be tuned for particular systems and can thus be more efficient than MD for obtaining equilibrium distributions. An interesting idea is to use MC simulations to obtain accurate initial guesses for subsequent MD simulations. Already as early as 1993, Venable and co-workers [68] used a scheme for efficiently sampling configurations of individual lipids in a mean field. These configurations were then used to develop the initial conditions for the molecular dynamic simulations. 

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. 

Tobias, D. J., Tu, K. and Klein, M. L. (1997). Atomic-scale molecular dynamics simulations of lipid membranes, Curr. Opin. Colloid Interf. Sci., 2, 15-26. 

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. 

Fattal, D. R. and Ben-Shaul, A. (1994). Mean-field calculations of chain packing and conformational statistics in lipid bilayers comparison with experiments and molecular dynamics studies, Biophys. J., 67, 983-995. 

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

Robinson, A. J., Richards, W. G., Thomas, P. J. and Hann, M. M. (1995). Behavior of cholesterol and its effect on head group and chain conformations in lipid bilayers a molecular dynamics study, Biophys. J., 68, 164-170. 

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