Biomembranes simulations

As it is assured that the conformations generated with the Marcelja field are consistent with experimental data, the procedure employing the overlay method and the continuous Marcelja model is a powerful tool for preparation of the initial coordinates of biomembrane simulations. By applying a short molecular dynamics simulation to the initial coordinates prepared by this procedure, the long equilibration time necessary to obtain results consistent with experiments is well circumvented. 

Experimental techniques based on the application of mechanical forces to single molecules in small assemblies have been applied to study the binding properties of biomolecules and their response to external mechanical manipulations. Among such techniques are atomic force microscopy (AFM), optical tweezers, biomembrane force probe, and surface force apparatus experiments (Binning et al., 1986 Block and Svoboda, 1994 Evans et ah, 1995 Israelachvili, 1992). These techniques have inspired us and others (see also the chapters by Eichinger et al. and by Hermans et al. in this volume) to adopt a similar approach for the study of biomolecules by means of computer simulations. 

Although extraction of lipids from membranes can be induced in atomic force apparatus (Leckband et al., 1994) and biomembrane force probe (Evans et al., 1991) experiments, spontaneous dissociation of a lipid from a membrane occurs very rarely because it involves an energy barrier of about 20 kcal/mol (Cevc and Marsh, 1987). However, lipids are known to be extracted from membranes by various enzymes. One such enzyme is phospholipase A2 (PLA2), which complexes with membrane surfaces, destabilizes a phospholipid, extracts it from the membrane, and catalyzes the hydrolysis reaction of the srir2-acyl chain of the lipid, producing lysophospholipids and fatty acids (Slotboom et al., 1982 Dennis, 1983 Jain et al., 1995). SMD simulations were employed to investigate the extraction of a lipid molecule from a DLPE monolayer by human synovial PLA2 (see Eig. 6b), and to compare this process to the extraction of a lipid from a lipid monolayer into the aqueous phase (Stepaniants et al., 1997). 

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... 

Alper, H. E. Stouch, T. R., Orientation and diffusion of a drug analogue in biomembranes molecular dynamics simulations, J. Phys. Chem. 1995, 99, 5724-5731. 

In biological membranes, the class of fully saturated PC lipids is just one of many. Indeed, variations in the lipid architecture are frequently encountered. There are variations with respect to the head-group structure as well as variations in the tail architecture. For example, in the tails, single or multiple unsaturated bonds are very common. There is relatively little knowledge about the role of lipid unsaturation in biomembranes. There are relatively few MD simulations on bilayers composed of lipids with unsaturated bonds. Nevertheless, single unsaturation as well as multiple unsaturated chains have been of some interest. For a recent review see reference [102], We will now present a selection of the results. We will also take this opportunity to compare the results from the MD simulations with those from the SCF calculations. 

We have already reported that synthetic peptide lipids, having ot-amino acid residuefs) interposed between a polar head moiety and a hydrophobic doublechain segment, can be used as models for functional simulation of biomembranes [23]. On this ground, we are to clarify molecular recognition specificity by supramolecular assemblies formed in combination of the macrocyclic receptors with the peptide lipid as artificial cell-surface receptors. 

Fig. 10.10. MD simulation results for a lamellar biomembrane and a typical spherical tenside micelle, respectively [122,123].

H. E. Alper and T. R. Stouch, Orientation and Diffusion of a Drug Analogue in Biomembranes Molecular Dynamics Simulations, J. Phys. Chem. 99 (1995) 5724. 

Lopez, C.F., Moore, P.B., Shelley, J.C., Shelley, M.Y. and Klein, M.L. (2002) Computer Simulation Studies of Biomembranes Using a Coarse Grain Model. Comput. Phys. Commun., 147, 1-6. 

Marcelja-Radic theory and its extensions (20-22) and Jonsson-Wennerstrom theory and its extensions (15-19) do not address the problem of the hydration force on the level of a detailed molecular Hamiltonian. Due to the complexity of the problem perhaps only a computer simulation technique can provide a description on this level. The tremendous usefulness of computer methods in the study of DNA and protein molecules (30, 31) inspires the hope that simulations will also play an important role in the study of biomembrane molecules. The first computer simulations to study the problem of hydration force on phospholipid molecules were performed by Scott (32, 33) and by Kjellander and Marcelja (34, 35). Because these studies were performed seven to eight years ago, the researchers were limited by the computer power available. As a result, the simulations were performed with... 

Leftin, A. and Brown, M.R 2011. An NMR database for simulations of membrane dynamics. Biochim. Biophys. Acta Biomembranes 1808 818-839. 

Lopez CF et al (2002) Computer simulation studies of biomembranes using a coarse grain model. ComputPhys Commun 147(l-2) l-6... 

Computational Studies of Biomembrane Systems Theoretical Considerations, Simulation Models, and Applications... 

Brannigan G, Lin L, Brown F (2006) Implicit solvent simulation models for biomembranes. 

Watson MC, Brandt EG, Welch PM, Brown FLH (2012) Determining biomembrane bending rigidities from simulations of modest size. Phys Rev Lett 109 028102... 

In the last decade, many efforts have been devoted to the study of the influence of chiral molecules on the enzymatic processes at the membrane surfaces. V -Acyl-L-and D-amino acid derivatives have been employed as model substances for simulating biomembranes and interfacial processes at biomembrane surfaces [32]. It has been found that chiral monolayers of V -acylamino acid methyl esters on a pure water surface showed that hydrogen bond formation via NH, COOH, and p-hydroxyphenyl groups (i.e., tyrosine side chains) lead to a pronounced chiral discrimination [33,34]. Homochiral (d-d or L-L interactions) and heterochiral (d-l interaction) discrimination can be observed depending on the area per molecule ( min)> which depends on the conformation of the amino acid residue and on the alkyl chain length. 

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