Lipid bilayer water dynamics

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 an artificial lipid bilayer of any size scale, it is a general feature that the bilayer acts as a two-dimensional fluid due to the presence of the water cushionlayer between the bilayer and the substrate. Due to this fluidic nature, molecules incorporated in the lipid bilayer show two-dimensional free diffusion. By applying any bias for controlling the diffusion dynamics, we can manipulate only the desired molecule within the artificial lipid bilayer, which leads to the development of a molecular separation system. 

One aspect of MD simulations is that all molecules, including the solvent, are specified in full detail. As detailed above, much of the CPU time in such a simulation is used up by following all the solvent (water) molecules. An alternative to the MD simulations is Brownian dynamics (BD) simulation. In this method, the solvent molecules are removed from the simulations. The effects of the solvent molecules are then reintroduced into the problem in an approximate way. Firstly, of course, the interaction parameters are adjusted, because the interactions should now include the effect of the solvent molecules. Furthermore, it is necessary to include a fluctuating force acting on the beads (atoms). These fluctuations represent the stochastic forces that result from the collisions of solvent molecules with the atoms. We know of no results using this technique on lipid bilayers. 

Venable, R. M., and Pastor, R. W. (2002). Molecular dynamics simulations of water wires in a lipid bilayer and water/octane model systems, J. Chem. Phys., 116, 2663-2664. 

The emission of Trp 19 in melittin shifts to the red side peaking at 341 nm (Fig. 18), and the probe location slightly moves away from the lipid interface toward the channel center. Consistently, we observed a larger fraction of the ultrafast solvation component (35%) and a smaller contribution of slow ordered-water motion (38%). Melittin consists of 26 amino acid residues (Fig. 9), and the first 20 residues are predominantly hydrophobic, whereas the other 6 near the carboxyl terminus are hydrophilic under physiological conditions. This amphipathic property makes melittin easily bound to membranes, and extensive studies from both experiments [156-161] and MD simulations [162-166] have shown the formation of an 7-helix at the lipid interface. Self-assembly of 7-helical melittin monomers is believed to be important in its lytic activity of membranes [167-169]. Our observed hydration dynamics are consistent with previous studies, which support the view that melittin forms an 7-helix and inserts into the lipid bilayers and leaves the hydrophilic C-terminus protruding into the water channel. The orientational relaxation shows a completely restricted motion of Trp 19, and the anisotropy is constant in 1.5 ns (Fig. 20b), which is consistent with Trp 19 located close to the interface around the headgroups and rigid well-ordered water molecules. 

Water-insoluble materials such as hydrophobic polymers can supply hydrophobic interfacial environments. However, molecular assemblies such as micelles and lipid bilayer vesicles are more advantageous, because they supply large surface areas that are in contact with a water phase and more flexible organization. These characteristics are advantageous for substrate incorporation and product release. As explained in Chap. 4, a lipid bilayer provides a more stable hydrophobic environment, while micelles provide more dynamic and less stable assembUes. Structural and orientational control between the... 

The exact dimensions of a phospholipid bilayer membrane in terms of the in-plane area and the height of the lipid molecules as well as the thickness of the water layer that is associated with them is dependent on the chemical identity of the phospholipid head group, the length and the degree of saturation of the acyl chains, and the degree of hydration. This information may be obtained from a combination of small-angle X-ray diffraction by MLV or oriented multi-bilayer samples of phospholipids in excess water, electron and/or neutron density profiles across lipid bilayers, and atomic level molecular dynamics simulations of hydrated lipid bilayers. H-NMR studies on selectively deuter-ated phospholipids have also been important in elucidating acyl... 

FIGURE 14.2 Molecular dynamics simulation of the diffusion of benzene within a hydrated lipid bilayer membrane. Benzene molecules are shown as Corey-Pauling-Koltun (CPK) models atoms in the phospholipid head groups are shown as ball and stick models and hydrocarbon chains and water molecules as dark and light stick models, respectively. (Reproduced with permission from Bassolino-Klinaas D, Alper HE, Stouch TR. Biochemistry 1993 32 12624-37.)... 

However, lipid bilayers are impermeable to ions and most polar molecules, with the exception of water, so they cannot, on their own, confer the multiple dynamic processes which we see in the function of biological membranes. All of this comes from proteins, inserted into the essentially inert backbone of the phospholipid bilayer (Figure 3.27), which mediate the multiple functions which we associate with biological membranes, such as molecular recognition by receptors, transport via pumps and channels, energy transduction, enzymes, and many more. Biomembranes are noncovalent assemblies of proteins and hpids, which can best be described as a fluid matrix, in which lipid (and protein molecules) can diffuse rapidly in the plane of the membrane, but not across it. 

The force calculation method described here promises to be of value in a variety of molecular mechanics simulations. It should be particularly useful in calculations on systems of high charge density, such as nucleic acids and lipid bilayers, where the accurate treatment of solvent by means of the explicit treatment of water molecules and ions is most computationally challenging. Preliminary calculations on small molecules show that the method can readily be incorporated into standard energy minimization and molecular dynamics computations. 

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