Molecular structure lipid bilayer

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. 

General anesthetics are usually small solutes with relatively simple molecular structure. As overviewed before, Meyer and Overton have proposed that the potency of general anesthetics correlates with their solubility in organic solvents (the Meyer-Overton theory) almost a century ago. On the other hand, local anesthetics widely used are positively charged amphiphiles in solution and reversibly block the nerve conduction. We expect that the partition of both general and local anesthetics into lipid bilayer membranes plays a key role in controlling the anesthetic potency. Bilayer interfaces are crucial for the delivery of the anesthetics. 

The phase transition of bilayer lipids is related to the highly ordered arrangement of the lipids inside the vesicle. In the ordered gel state below a characteristic temperature, the lipid hydrocarbon chains are in an all-trans configuration. When the temperature is increased, an endothermic phase transition occurs, during which there is a trans-gauche rotational isomerization along the chains which results in a lateral expansion and decrease in thickness of the bilayer. This so-called gel to liquid-crystalline transition has been demonstrated in many different lipid systems and the relationship of the transition to molecular structure and environmental conditions has been studied extensively. 

One of the key parameters for correlating molecular structure and chemical properties with bioavailability has been transcorneal flux or, alternatively, the corneal permeability coefficient. The epithelium has been modeled as a lipid barrier (possibly with a limited number of aqueous pores that, for this physical model, serve as the equivalent of the extracellular space in a more physiological description) and the stroma as an aqueous barrier (Fig. 11). The endothelium is very thin and porous compared with the epithelium [189] and often has been ignored in the analysis, although mathematically it can be included as part of the lipid barrier. Diffusion through bilayer membranes of various structures has been modeled for some time [202] and adapted to ophthalmic applications more recently [203,204]. For a series of molecules of similar size, it was shown that the permeability increases with octa-nol/water distribution (or partition) coefficient until a plateau is reached. Modeling of this type of data has led to the earlier statement that drugs need to be both... 

The relationships between the molecular structure of environmental pollutants, such as polychlorinated biphenyls (PCBs), and their rate of biodegradation are still not well understood, though some empirical relationships have been established. Self-organizing maps (SOMs) have been used to rationalize the resistance of PCBs to biodegradation and to predict the susceptibility to degradation of those compounds for which experimental data are lacking.3 The same technique has been used to analyze the behavior of lipid bilayers, following a... 

Myelin in situ has a water content of about 40%. The dry mass of both CNS and PNS myelin is characterized by a high proportion of lipid (70-85%) and, consequently, a low proportion of protein (15-30%). By comparison, most biological membranes have a higher ratio of proteins to lipids. The currently accepted view of membrane structure is that of a lipid bilayer with integral membrane proteins embedded in the bilayer and other extrinsic proteins attached to one surface or the other by weaker linkages. Proteins and lipids are asymmetrically distributed in this bilayer, with only partial asymmetry of the lipids. The proposed molecular architecture of the layered membranes of compact myelin fits such a concept (Fig. 4-11). Models of compact myelin are based on data from electron microscopy, immunostaining, X-ray diffraction, surface probes studies, structural abnormalities in mutant mice, correlations between structure and composition in various species, and predictions of protein structure from sequencing information [4]. 

Let us first consider the lipid molecular structures required. First is the hydrophobic matching. The length of the hydrophobic chain determines the thickness of the hydrophobic part of the lipid bilayer, this should correspond closely to the dimension of the native membrane. As most biological membranes contain diacylglycerol lipids with hydrophobic chain lengths of 16 18 carbon atoms. Thus, synthetic lipids should possess relatively long hydrocarbon chain length, e.g., 16-18 carbon atoms. 

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. 

Although varying considerably in molecular size, any GPCR polypeptide sequence contains seven hydrophobic a-helices that span the lipid bilayer and dictate the typical macromolecule architecture. Seven transmembrane domains bundled up to form a polar internal tunnel and expose the N-terminus and three interconnecting loops, to the exterior, and the C-terminus with a matching number of loops, to the interior of the cell [1-3]. This structural information was recently confirmed by the resolution of the crystal structure of rhodopsin [4,5]. 

Fig. 8 Proposed model for gramicidin S in a membrane according to the orientational constraints obtained from and N-NMR. The upright backbone alignment (r 80°) and slant of the /3-sheets (p -45°) are compatible with the formation of an oligomeric /3-barrel that is stabilized by hydrogen bonds (dotted lines). A The oligomer is depicted sideways from within the lipid bilayer interior (showing only backbone atoms for clarity, but with hydrophobic side chains added to one of the monomers). Atomic coordinates of GS were taken from a monomeric structure [4], and the two DMPC lipid molecules are drawn to scale (from a molecular dynamics simulation coordinate file). The bilayer cross-section is coloured yellow in its hydrophobic core, red in the amphiphilic regions, and light blue near the aqueous surface. B Illustrates a top view of the putative pore, although the number of monomers remains speculative...

Afonin S (2004) Structural studies on membrane-active peptides in lipid bilayers by solid state F-NMR. PhD thesis. Institute of Molecular Biology. Friedrich-Schiller-Universitat, Jena, p 98... 

The Guy open conformation model docked structure was minimized in vacuo followed by a 1-ns molecular dynamics simulation of the complex embedded in a phosphatidylethanolamine (POPE) lipid bilayer. Adjustments were made to the model, and simulations were repeated so that very little movement occurred during the hnal iterations. Similar methods were used to dock the two domains in transitional and resting states. However, these results are more tenuous as little experimental data is available. In particular, the position of the S4-S5 linker and its role in opening and closing the pore are uncertain. The supplemental movie accompanying reference 36 illustrates the open-to-close-to-open cycle resulting from the simulations. 

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