Membrane molecular dynamics simulation

H4 receptor an explicit membrane molecular dynamics simulation study. Journal of Chemical Information and Modeling, 48 (6), 1199-1210. 

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). 

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. 

PERMEATION OF LIPID MEMBRANES MOLECULAR DYNAMICS SIMULATIONS... 

Permeation of Lipid Membranes Molecular Dynamics Simulations... 

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. 

H. Kovacs, A.E. Mark, J. Johansson, and W.F. van Gunsteren. The effect of environment on the stability of an integral membrane helix Molecular dynamics simulations of surfactant protein C in chloroform, methanol and water. J. Mol. Biol, 247 808-822, 1995. 

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. 

In a normal molecular dynamics simulation with repeating boundary conditions (i.e., periodic boundary condition), the volume is held fixed, whereas at constant pressure the volume of the system must fluemate. In some simulation cases, such as simulations dealing with membranes, it is more advantageous to use the constant-pressure MD than the regular MD. Various schemes for prescribing the pressure of a molecular dynamics simulation have also been proposed and applied [23,24,28,29]. In all of these approaches it is inevitable that the system box must change its volume. 

II. MOLECULAR DYNAMICS SIMULATIONS OF MEMBRANES A. System Size and Construction... 

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. 

For any even vaguely realistic atomically constituted membrane it is unlikely that any theory will become available in the near future which will properly or reasonably describe the dynamic properties of the membrane, the fluids near it, and their passage, or selective passage, through it. Nevertheless, one should continue trying with simple models and simple theories [39-43], which show the way forward and can, as usual, be tested by the virtually exact results of molecular dynamics simulation. 

Chapter 15 gives an extensive and detailed review of theoretical and practical aspects of macromolecular transport in nanostructured media. Chapter 16 examines the change in transport properties of electrolytes confmed in nanostructures, such as pores of membranes. The confinment effect is also analyzed by molecular dynamic simulation. 

Further progress in understanding membrane instability and nonlocality requires development of microscopic theory and modeling. Analysis of membrane thickness fluctuations derived from molecular dynamics simulations can serve such a purpose. A possible difficulty with such analysis must be mentioned. In a natural environment isolated membranes assume a stressless state. However, MD modeling requires imposition of special boundary conditions corresponding to a stressed state of the membrane (see Refs. 84,87,112). This stress can interfere with the fluctuations of membrane shape and thickness, an effect that must be accounted for in analyzing data extracted from computer experiments. 

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. 

Bassolino-Klimas, D. Alper, H. E. Stouch, T. R., Drug-membrane interactions studied by molecular dynamics simulation size dependence of diffusion, Drug Des. Discov. 1996,13, 135-141. 

Guba, W. and Kessler, H. A novel computational mimetic of biological membranes in molecular dynamics simulations, J.Phys.Chem., 98 (1994). 23-27... 

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. 

---