Molecular Dynamics Simulation of Conformational Flexibility of Alamethicin Fragments in Aqueous and Membranous Environment

Abstract

We present here results on molecular dynamics (MD) simulation on two fragments of channel forming antibiotic peptide Alamethicin, containing isoamino butyric acid (Aib). Simulations are carried out in aqueous and membranous environment in a bilayer of 39 molecules of Dimyristoyl phosphatidyl choline (DMPC). The peptides Boc—;Pro-Aib-Ala-Aib- OBzl (Alam 1) and Boc-Leu-Aib-Pro-OBzl (Alam 2) were simulated from their crystallography coordinates. The bilayers were built from two different conformations (A and B) of DMPC reported in crystal data. The P-N dipoles were arranged hexagonally with surface area per lipid molecule 66.5 A°² and P-P separation across the bilayer 34 A°. They were hydrated by 28.6 and 25.5 water molecules per DMPC molecule. Simulations are done using AMBER 4.0 package in constant number volume temperature (NVT) condition for 100 pico seconds (ps) in aqueous environment and 250 ps of equilibrated bilayer. Geometric parameters of lipids as: bilayer thickness, order parameter of the chains, transfraction of chain torsional angles were monitored. We also monitored geometric parameters of the peptides as backbone torsional angles, distances amongst Ca atoms, angles between Cα atoms, movement of center of gravity (CG) along and perpendicular to bilayer normal. We find that membrane bilayer is slightly disturbed due to the presence of peptides. In case of alam 2 in water angles ψ1 and ψ3 showed larger variation in water compared to same in the bilayer. The peptide conformation is more stable in DMPC bilayer. However the peptides showed movement along and perpendicular to bilayer normal. This we believe is due to hydrophobic nature of these peptides.     

Conformation of nifedipine in hydrated 1,2-di-myristoyl-sn-glycero-3-phosphorylcholine bilayer molecular dynamics simulation

The conformation of nifedipine, a cardiac and smooth muscle calcium ion channel antagonist is studied in a hydrated bilayer of forty nine 1,2-di-myristoyl-sn-glycero-3-phosphorylcho-line (DMPC) molecules using molecular dynamics (MD) simulation technique. The simulation was carried out in conditions of constant number, volume and temperature (NVT) at 310 K, which is above the liquid crystalline (Lα) transition temperature of DMPC. The periodic boundary conditions were applied in three-dimensions. Thus the model represented an infinite bilayer. The important geometric parameters characteristic to DMPC and nifedipine molecules were calculated and compared with other theoretical and experimental results pertaining to nifedipine and other related dihydrophyridine (DHP) analogues. Our results suggest that conformational parameters required for antagonist activity are fairly conserved during the interaction of nifedipine with DMPC bilary and bilayer stabilizes the drug conformation in the bioactive form.     

The influence of cholesterol on interactions and dynamics of ibuprofen in a lipid bilayer

In this work, molecular dynamics (MD) simulations with atomistic details were performed to examine the influence of the cholesterol on the interactions and the partitioning of the hydrophobic drug ibuprofen in a fully hydrated 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayer. Analysis of MD simulations indicated that ibuprofen molecules prefer to be located in the hydrophobic acyl chain region of DMPC/cholesterol bilayers. This distribution decreases the lateral motion of lipid molecules. The presence of ibuprofen molecules in the bilayers with 0 and 25 mol% cholesterol increases the ordering of hydrocarbon tails of lipids whereas for the bilayers with 50 mol% cholesterol, ibuprofen molecules perturb the flexible chains of DMPC lipids which leads to the reduction of the acyl chain order parameter. The potential of the mean force (PMF) method was used to calculate the free energy profile for the transferring of an ibuprofen molecule from the bulk water into the DMPC/cholesterol membranes. The PMF studies indicated that the presence of 50 mol% cholesterol in the bilayers increases the free energy barrier and slows down the permeation of the ibuprofen drug across the DMPC bilayer. This can be due to the condensing and ordering effects of the cholesterol on the bilayer.     

A Molecular Dynamics Study of DMPC Lipid Bilayers Interacting with Dimethylsulfoxide–Water Mixtures

The diffusion process of dimethylsulfoxide (DMSO) through zwitterionic dimyristoylphosphatidylcholine (DMPC) lipid bilayer was studied by means of molecular dynamics (MD) simulations. To account for the cryoprotectant concentration difference between the inside and the outside of the cell, dual DMPC lipid bilayers which separate two aqueous reservoirs with and without DMSO were modeled. The initial configuration of the simulation model had DMSO molecules present in one of the aqueous phases (outside the cell) at two different concentrations of ~3 and ~6?mol%. MD simulations were performed on the systems for 50?ns at 323?K and 1?bar. Although the simulation time considered in the study was insufficient for the DMSO molecules to reach the other aqueous phase and equilibrium, early stages of the diffusion process indicated that DMSO molecules had a tendency to diffuse towards the other aqueous phase. The effects of DMSO on bilayer structural characteristics during the diffusion process were investigated. Simulations were analyzed to correlate the following properties of lipid bilayers in the presence of two different aqueous phases: area per lipid, lipid thickness, mass density profiles, lipid tail order parameter and water dipole orientation. Area per lipid calculated for the leaflet facing the aqueous DMSO?Cwater mixture did not show any significant difference compared to area per lipid for the DMSO-free pure DMPC bilayer. Mass density profiles revealed that DMSO molecules had a strong tendency to diffuse toward the aqueous phase with pure water. The lipid tail order parameter calculated for the sn-1 tail of the leaflet facing the aqueous DMSO?Cwater mixture showed that the ordering of lipid tails decreased compared to the leaflet exposed to pure water. However, the ordering of lipid tails in a system where a single bilayer is hydrated by an aqueous DMSO?Cwater mixture is far lower.     

Combined monte carlo and molecular dynamics simulation of fully hydrated dioleyl and palmitoyl-oleyl phosphatidylcholine lipid bilayers

We have applied a new equilibration procedure for the atomic level simulation of a hydrated lipid bilayer to hydrated bilayers of dioleyl-phosphatidylcholine (DOPC) and palmitoyl-oleyl phosphatidylcholine (POPC). The procedure consists of alternating molecular dynamics trajectory calculations in a constant surface tension and temperature ensemble with configurational bias Monte Carlo moves to different regions of the configuration space of the bilayer in a constant volume and temperature ensemble. The procedure is applied to bilayers of 128 molecules of POPC with 4628 water molecules, and 128 molecules of DOPC with 4825 water molecules. Progress toward equilibration is almost three times as fast in central processing unit (CPU) time compared with a purely molecular dynamics (MD) simulation. Equilibration is complete, as judged by the lack of energy drift in 200-ps runs of continuous MD. After the equilibrium state was reached, as determined by agreement between the simulation volume per lipid molecule with experiment, continuous MD was run in an ensemble in which the lateral area was restrained to fluctuate about a mean value and a pressure of 1 atm applied normal to the bilayer surface. Three separate continuous MD runs, 200 ps in duration each, separated by 10,000 CBMC steps, were carried out for each system. Properties of the systems were calculated and averaged over the three separate runs. Results of the simulations are presented and compared with experimental data and with other recent simulations of POPC and DOPC. Analysis of the hydration environment in the headgroups supports a mechanism by which unsaturation contributes to reduced transition temperatures. In this view, the relatively horizontal orientation of the unsaturated bond increases the area per lipid, resulting in increased water penetration between the headgroups. As a result the headgroup-headgroup interactions are attenuated and shielded, and this contributes to the lowered transition temperature.     

Dynamic chain conformations in dimyristoyl glycerol-dimyristoyl phosphatidylcholine mixtures. 2H-NMR studies.

The dynamic molecular lipid chain conformations in fully hydrated dimyristoyl phosphatidylcholine (DMPC)-dimyristoyl glycerol (DMG) mixtures have been investigated by 2H-NMR spectroscopy of the individual lipid components, the sn-2 chains of which were perdeuterated or, in the case of DMG, specifically deuterated at the C-2 position. Mixtures of compositions corresponding to the three different regions of the binary phase diagram in which the fluid phase is lamellar (DMPC:DMG 70:30 mol/mol), inverted hexagonal (DMPC:DMG 45:55 and 40:60 mol/mol), or isotropic (DMPC:DMG 20:80 mol/mol) were investigated. The gel phase in all three regions of the phase diagram has a lamellar structure, with the lipid chains rotating about the molecular long axis but executing only limited angular excursions. In the fluid lamellar phase of the 70:30 mol/mol DMPC-DMG mixture the profile of segmental chain flexibility is similar to that in single-component phospholipid bilayers and is characterized by an order parameter plateau for both lipid components. The chain order of the DMPC component is greater than in bilayers of DMPC alone and is also greater than that of the DMG component. In the inverted hexagonal phase of the 45:55 mol/mol DMPC-DMG mixture the chain flexibility profile is characterized by more widely spaced segmental order parameters off the plateau region. The intrinsic degree of chain order in the inverted hexagonal phase is less than in the lamellar phase of the 70:30 mol/mol mixture, and the difference in chain order between the DMPC and DMG components is reduced relative to that in the lamellar phase. The unique conformational features at the C-2 position of the sn-2 chain that characterize bilayers of diacyl phospholipids are found also for the diacylglycerol molecules in the fluid lamellar phase and most probably also in the inverted hexagonal phase. The DMG molecules are therefore integrated in the membrane (or nonlamellar lipid phase) in a configuration that is similar to that of the phospholipids and different from the crystal structure of diacylglycerols.     

Investigation of phase transitions of saturated phosphocholine lipid bilayers via molecular dynamics simulations

Lipid bilayers play an important role in biological systems as they protect cells against unwanted chemicals and provide a barrier for material inside a cell from leaking out. In this paper, nearly 30 μs of molecular dynamics (MD) simulations were performed to investigate phase transitions of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dipalmitoyl-sn-glycero-phosphocholine (DPPC) lipid bilayers from the liquid crystalline (L_α) to the ripple (P_β) and to the gel phase (L_β). Our MD simulations accurately predict the main transition temperature for the single-component bilayers. A key focus of this work is to quantify the structure of the P_β phase for DMPC and compare with measures from x-ray experiments. The P_β major arm has similar structure to that of the L_β, while the thinner minor arm has interdigitated chains and the transition region between these two regions has large chain splay and disorder. At lower temperatures, our MD simulations predict the formation of the L_β phase with tilted fatty acid chains. The P_β and L_β phases are studied for mixtures of DMPC and DPPC and compare favorably with experiment. Overall, our MD simulations provide evidence for the relevancy of the CHARMM36 lipid force field for structures and add to our understanding of the less-defined P_β phase.     

Orientation and lipid-peptide interactions of gramicidin A in lipid membranes: polarized attenuated total reflection infrared spectroscopy and spin-label electron spin resonance

Gramicidin A was incorporated at a peptide/lipid ratio of 1:10 mol/mol in aligned bilayers of dimyristoyl phosphatidylcholine (DMPC), phosphatidylserine (DMPS), phosphatidylglycerol (DMPG), and phosphatidylethanolamine (DMPE), from trifluoroethanol. Orientations of the peptide and lipid chains were determined by polarized attenuated total reflection infrared spectroscopy. Lipid-peptide interactions with gramicidin A in DMPC bilayers were studied with different spin-labeled lipid species by using electron spin resonance spectroscopy. In DMPC membranes, the orientation of the lipid chains is comparable to that in the absence of peptide, in both gel and fluid phases. In gel-phase DMPC, the effective tilt of the peptide exceeds that of the lipid chains, but in the fluid phase both are similar. For gramicidin A in DMPS, DMPG, and DMPE, the degree of orientation of the peptide and lipid chains is less than in DMPC. In the fluid phase of DMPS, DMPG, and DMPE, gramicidin A is also less well oriented than are the lipid chains. In DMPE especially, gramicidin A is largely disordered. In DMPC membranes, three to four lipids per monomer experience direct motional restriction on interaction with gramicidin A. This is approximately half the number of lipids expected to contact the intramembranous perimeter of the gramicidin A monomer. A selectivity for certain negatively charged lipids is found in the interaction with gramicidin A in DMPC. These results are discussed in terms of the integration of gramicidin A channels in lipid bilayers, and of the interactions of lipids with integral membrane proteins.     

Experimental and theoretical studies of emodin interacting with a lipid bilayer of DMPC

Emodin is one of the most abundant anthraquinone derivatives found in nature. It is the active principle of some traditional herbal medicines with known biological activities. In this work, we combined experimental and theoretical studies to reveal information about location, orientation, interaction and perturbing effects of Emodin on lipid bilayers, where we have taken into account the neutral form of the Emodin (EMH) and its anionic/deprotonated form (EM^?). Using both UV/Visible spectrophotometric techniques and molecular dynamics (MD) simulations, we showed that both EMH and EM^? are located in a lipid membrane. Additionally, using MD simulations, we revealed that both forms of Emodin are very close to glycerol groups of the lipid molecules, with the EMH inserted more deeply into the bilayer and more disoriented relative to the normal of the membrane when compared with the EM^?, which is more exposed to interfacial water. Analysis of several structural properties of acyl chains of the lipids in a hydrated pure DMPC bilayer and in the presence of Emodin revealed that both EMH and EM^? affect the lipid bilayer, resulting in a remarkable disorder of the bilayer in the vicinity of the Emodin. However, the disorder caused by EMH is weaker than that caused by EM^?. Our results suggest that these disorders caused by Emodin might lead to distinct effects on lipid bilayers including its disruption which are reported in the literature.     

Trifonov's Meta-Definition of Life

Abstract

We present here results on 260 pico seconds (ps) molecular dynamics (MD) simulation of substance P (SP) in hydrated bilayer of dimyristoyl phosphatidyl choline (DMPC) (39 molecules of DMPC with 776 water molecules). 260 ps MD simulation has been carried out in 0.001 ps time interval with united atom force field, using AMBER 4.0 package. Non bonded pair list was updated every 20 cycles using 12.5 Å cut off distance. Analysis of MD data is done using our package ANALMD. The obtained models are presented using graphics package RASMOL. All simulations, analysis of MD data and graphics is done on INDIGO-2, R-4400 extreme graphics work station. Our results show no systematic change in order parameter, but reduction in transfraction of the chain torsional angles, compared to our earlier results on MD simulation on hydrated DMPC bilayer without SP. C-terminal and central peptide residues adopt partial helical conformation. Helix type as classified on the basis of H-bonds is between a and 3₁₀. The peptide backbone shows flexibility during heating runs. Later, it is stabilized and there was not much change in the spatial position of the backbone. Lipid matrix serves the role of immobilization of the peptide backbone in a preferred conformation.     

Effect of lipid composition on the "membrane response" induced by a fusion peptide

To understand the initial stages of membrane destabilization induced by viral proteins, the factors important for binding of fusion peptides to cell membranes must be identified. In this study, effects of lipid composition on the mode of peptides' binding to membranes are explored via molecular dynamics (MD) simulations of the peptide E5, a water-soluble analogue of influenza hemagglutinin fusion peptide, in two full-atom hydrated lipid bilayers composed of dimyristoyl- and dipalmitoylphosphatidylcholine (DMPC and DPPC, respectively). The results show that, although the peptide has a common folding motif in both systems, it possesses different modes of binding. The peptide inserts obliquely into the DMPC membrane mainly with its N-terminal alpha helix, while in DPPC, the helix lies on the lipid/water interface, almost parallel to the membrane surface. The peptide seriously affects structural and dynamical parameters of surrounding lipids. Thus, it induces local thinning of both bilayers and disordering of acyl chains of lipids in close proximity to the binding site. The "membrane response" significantly depends upon lipid composition: distortions of DMPC bilayer are more pronounced than those in DPPC. Implications of the observed effects to molecular events on initial stages of membrane destabilization induced by fusion peptides are discussed.     

Structure and dynamics of the dilauroylphosphatidylethanolamine lipid bilayer.

A 200-ps molecular dynamics (MD) simulation trajectory of a model dilauroylphosphatidylethanolamine (DLPE) bilayer in water at 315 K has been generated. Segmental order parameters, electron density profiles, and water pair distribution functions have been calculated. Comparison to experiment is made where possible. The dynamics of the system has been studied by analyzing the velocity autocorrelation functions (VAF) of both water and lipid atoms. Furthermore, the diffusive properties of water have been analyzed by computing the mean square displacement (MSD) and orientational correlation function (OCF) of water in two regions around the bilayer. The calculated order parameters show a behavior similar to the liquid crystalline phase of other bilayers, but the region around C1-C3 does not show the expected behavior. The electron density profile shows features that are characteristic of the liquid crystalline phase. The radial distribution functions suggest ordering of water near the charged head groups, which results in about 15 water molecules solvating each lipid molecule. We find from the VAF, MSD, and OCF calculation that the water molecules near the head groups of the lipid bilayer move more slowly than those further away. The VAF of the hydrocarbon chains have features of low-frequency motions that are probably cooperative nature in addition to the high-frequency motions associated with bond angle and torsional motions.     

Effect of cholesterol on the structure and dynamic properties of unsaturated phospholipid bilayers

Molecular dynamics (MD) computer simulations of five different hydrated unsaturated phosphatidylcholine lipid bilayers built up by 18:0/18:1(n-9)cis PC, 18:0/18:2(n-6)cis PC, 18:0/18:3(n-3)cis PC, 18:0/20:4(n-6)cis PC, and 18:0/22:6(n-3)cis PC molecules with 40 mol% cholesterol, and the same five pure phosphatidylcholine bilayers have been performed at 303 K. The simulation box of a lipid bilayer contained 96 phosphatidylcholines, 64 cholesterols, and 3840 water molecules (48 phosphatidylcholine molecules and 32 cholesterols per layer and 24 water molecules per phospholipid or cholesterol in each case). The lateral self-diffusion coefficients of the lipids in these systems and mass density profiles with respect to the bilayer normal have been analyzed. It has been found that the lateral diffusion coefficients of phosphatidylcholine molecules increase with increasing number of double bonds in one of the lipid chains, both in pure bilayers and in bilayers with cholesterol. It has been found as well that the lateral diffusion coefficient of phosphatidylcholine molecules of a lipid bilayer with 40 mol% cholesterol is smaller than that for the corresponding pure phosphatidylcholine bilayer.     

Liquid ordered and gel phases of lipid bilayers: fluorescent probes reveal close fluidity but different hydration

Hydration and fluidity of lipid bilayers in different phase states were studied using fluorescent probes selectively located at the interface. The probe of hydration was a recently developed 3-hydroxyflavone derivative, which is highly sensitive to the environment, whereas the probe of fluidity was the diphenylhexatriene derivative, 1-[4-(trimethylamino)phenyl]-6-phenylhexa-1,3,5-triene. By variation of the cholesterol content and temperature in large unilamellar vesicles composed of sphingomyelin or dipalmitoylphosphatidlycholine, we generated different phases: gel, liquid ordered (raft), liquid crystalline, and liquid disordered (considered as liquid crystalline phase with cholesterol). For these four phases, the hydration increases in the following order: liquid ordered < gel approximately liquid disordered < liquid crystalline. The membrane fluidity shows a somewhat different trend, namely liquid ordered approximately gel < liquid disordered < liquid crystalline. Thus, gel and liquid ordered phases exhibit similar fluidity, whereas the last phase is significantly less hydrated. We expect that cholesterol due to its specific H-bonding interactions with lipids and its ability to fill the voids in lipid bilayers expels efficiently water molecules from the highly ordered gel phase to form the liquid ordered phase. In this study, the liquid ordered (raft) and gel phases are for the first time clearly distinguished by their strong difference in hydration.     

Lipid hydration and mobility: an interplay between fluorescence solvent relaxation experiments and molecular dynamics simulations

Fluorescence solvent relaxation experiments are based on the characterization of time-dependent shifts in the fluorescence emission of a chromophore, yielding polarity and viscosity information about the chromophore’s immediate environment. A chromophore applied to a phospholipid bilayer at a well-defined location (with respect to the z-axis of the bilayer) allows monitoring of the hydration and mobility of the probed segment of the lipid molecules. Specifically, time-resolved fluorescence experiments, fluorescence quenching data and molecular dynamic (MD) simulations show that 6-lauroyl-2-dimethylaminonaphthalene (Laurdan) probes the hydration and mobility of the sn-1 acyl groups in a phosphatidylcholine bilayer. The time-dependent fluorescence shift (TDFS) of Laurdan provides information on headgroup compression and expansion induced by the addition of different amounts of cationic lipids to phosphatidylcholine bilayers. Those changes were predicted by previous MD simulations. Addition of truncated oxidized phospholipids leads to increased mobility and hydration at the sn-1 acyl level. This experimental finding can be explained by MD simulations, which indicate that the truncated chains of the oxidized lipid molecules are looping back into aqueous phase, hence creating voids below the glycerol level. Fluorescence solvent relaxation experiments are also useful in understanding salt effects on the structure and dynamics of lipid bilayers. For example, such experiments demonstrate that large anions increase hydration and mobility at the sn-1 acyl level of phosphatidylcholine bilayers, an observation which could not be explained by standard MD simulations. If polarizability is introduced into the applied force field, however, MD simulations show that big soft polarizable anions are able to interact with the hydrophilic/hydrophobic interface of the lipid bilayer, penetrating to the level probed by Laurdan, and that they expand and destabilize the bilayer making it more hydrated and mobile.     

Constructing the suitable initial configuration of the membrane-protein system in molecular dynamics simulations

A method for constructing the suitable initial configuration of the membrane-protein system for molecular dynamics (MD) simulations is presented. This method could provide some hydrated initial configurations and help us to determine the best surface area of the system by contracting the surface area and comparing the optimized lowest energy of the system by energy minimization. The gramicidin A (GA) channel in;the fully hydrated dimyristoylphosphatidylcholine (DMPC) bilayer was used as our model. Three configurations with different surface areas were selected and applied for one 400 ps and two 300 ps MD simulations at constant pressure and temperature. All simulations were fairly stable without any constraints. Through analysis of the MD trajectories we found that the system with the best surface area was more stable than the other two systems, whose sizes were changed in the simulations. Further analysis of the bilayer normal length and the order parameters of the lipid alkyl tails indicates that the system with the best surface area shows some characteristics of the L_α phase, while both the smaller and the larger size systems have distinct deviations from the L_α phase that we expect. This illustrates that the correct surface area and the suitable initial configuration have an important influence on the phase of the membrane in the MD simulation. In addition, by comparing the root mean square differences of GA relative to the initial structure and interaction energy between different components of the system for all three systems, we find that the state of the DMPC bilayer has exerted a significant influence on the structure of GA. All these results demonstrate the validity of our method for constructing the initial configuration of the membrane-protein system for MD simulations. Received: 10 September 1998 / Revised version: 19 March 1999 / Accepted: 19 March 1999     

Solid‐state NMR and simulation studies of equinatoxin II N‐terminus interaction with lipid bilayers

The interaction with model membranes of a peptide, EqtII_1–32, corresponding to the N‐terminal region of the pore‐forming toxin equinatoxin II (EqtII) has been studied using solid‐state NMR and molecular dynamics (MD) simulations. The distances between specifically labeled nuclei in [¹⁹F‐para]Phe16‐[1‐¹³C]Leu19 and [¹⁹F‐para]Phe16‐[¹⁵N]Leu23 analogs of EqtII_1–32 measured by REDOR in lyophilized peptide were in agreement with published crystal and solution structures. However, in both DMPC and mixed DMPC:SM membrane environments, significant changes in the distances between the labeled amino acid pairs were observed, suggesting changes in helical content around the experimentally studied region, 16–23, in the presence of bilayers. ¹⁹F‐³¹P REDOR experiments indicated that the aromatic ring of Phe16 is in contact with lipid headgroups in both membrane environments. For the DMPC:SM mixed bilayers, a closer interaction between Phe16 side chains and lipid headgroups was observed, but an increase in distances was observed for both labeled amino acid pairs compared with those measured for EqtII_1–32 in pure DMPC bilayers. The observed differences between DMPC and DMPC:SM bilayers may be due to the greater affinity of EqtII for the latter. MD simulations of EqtII_1–32 in water, on a pure DMPC bilayer, and on a mixed DMPC:SM bilayer indicate significant peptide secondary structural differences in the different environments, with the DMPC‐bound peptide adopting helical formations at residues 16–24, whereas the DMPC:SM‐bound peptide exhibits a longer helical stretch, which may contribute to its enhanced activity against PC:SM compared with pure PC bilayers. Proteins 2010. © 2009 Wiley‐Liss, Inc.     

Combined Monte Carlo and molecular dynamics simulation of hydrated lipid-cholesterol lipid bilayers at low cholesterol concentration

We have applied a hybrid equilibration and sampling procedure for the atomic level simulation of a hydrated lipid bilayer to systems consisting of dipalmitoyl phosphatidylcholine (DPPC) and cholesterol, and palmitoyl-oleyl phosphatidylcholine (POPC) at low (approximately 6%) cholesterol concentration. The procedure is applied to bilayers of 94 molecules of DPPC, 6 molecules of cholesterol, and 3205 water molecules, and to bilayers of 120 molecules of POPC, 8 molecules of cholesterol, and 4268 water molecules, at a temperature of 325 K. After equilibration, three separate 400-ps continuous molecular dynamics runs, separated by 10,000 configurational bias Monte Carlo steps, were carried out for each system. Properties of the systems were calculated and averaged over the three separate runs. Results of the simulations are presented and compared with experimental data and with other recent simulations of DPPC and cholesterol, and of pure DPPC, and pure POPC. Certain properties of the bilayers are indistinguishable from cholesterol-free bilayers, including lateral diffusion and electron density. Other properties, most notably the order parameter profile, show the effect of cholesterol even at low concentrations.     

Structural aspects of pressure effects on infrared spectra of mixed-chain phosphatidylcholine assemblies in D2O

The barotropic behavior of D2O dispersions of 1-stearoyl-2-caproyl-sn-glycero-3-phosphocholine, C(18):C(10)PC, a highly asymmetric phospholipid in which the length of the fully extended acyl chain at the sn-1 position of the glycerol backbone is twice as long as that at the sn-2 position, has been investigated by high-pressure Fourier transform infrared spectroscopy. This asymmetric phosphatidylcholine bilayer at room temperature displays a pressure-induced phase transition corresponding to the liquid-crystalline----gel phase transition at 1.4 kbar. A conformational ordering of the lipid acyl chains is observed to take place abruptly at the transition pressure of 1.4 kbar. However, the lamellar lipid molecules and their acyl chains remain to be orientationally disordered in the gel phase until the applied pressure reaches 5.5 kbar. In the gel phase of fully hydrated C(18):C(10)PC, the asymmetric lipid molecules assemble into mixed interdigitated bilayers with perpendicular orientation of the zigzag planes among neighboring acyl chains. The role of excess water played in the interchain structure and the behavior of excess water and bound water under high pressure are also discussed.     

Molecular dynamics study of changes in physico-chemical properties of DMPC lipid bilayers by addition of nonionic surfactant C12E10

Changes in physico-chemical properties of dimyristoyl phosphatidylcholine (DMPC) lipid bilayers caused by the addition of 9.4 mol% nonionic surfactant decaoxyethylene monododecyl ethers (C₁₂E₁₀) have been investigated by molecular dynamics calculations. In spite of addition of single chain C₁₂E₁₀, the lipid bilayers showed an increase of membrane area. Isothermal area compressibility, which is a measure of membrane softness in lateral direction, also increased by 50% for DMPC/C₁₂E₁₀ mixed bilayers. Furthermore, the order parameter of C–H vector for DMPC acyl tails decreased. We found that these changes are caused by the hydrophilic head groups of C₁₂E₁₀ which are located near the glycerol backbone of the DMPC molecules and have bulky random coil conformation without any preferential ordered structures.