Partial interdigitation of lipid bilayers (original) (raw)
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Structural effects of small molecules on phospholipid bilayers investigated by molecular simulations
Fluid Phase Equilibria, 2005
We summarize and compare recent molecular dynamics simulations on the interactions of dipalmitoylphosphatidylcholine (DPPC) bilayers in the liquid crystalline phase with a number of small molecules including trehalose, a disaccharide of glucose, alcohols, and dimethylsulfoxide (DMSO). The sugar molecules tend to stabilize the structure of the bilayer as they bridge adjacent lipid headgroups. They do not strongly change the structure of the bilayer. Alcohols and DMSO destabilize the bilayer as they increase its area per molecule in the bilayer plane and decrease the order parameter. Alcohols have a stronger detrimental effect than DMSO. The observables which we compare are the area per molecule in the plane of the bilayer, the membrane thickness, and the nuclear magnetic resonance (NMR) order parameter of DPPC hydrocarbon tails. The area per molecule and the order parameter are very well correlated whereas the bilayer thickness is not necessarily correlated with them.
Molecular dynamics simulation studies of lipid bilayer systems
Acta biochimica Polonica, 2000
The main structural element of biological membranes is a liquid-crystalline lipid bilayer. Other constituents, i.e. proteins, sterols and peptides, either intercalate into or loosely attach to the bilayer. We applied a molecular dynamics simulation method to study membrane systems at various levels of compositional complexity. The studies were started from simple lipid bilayers containing a single type phosphatidylcholine (PC) and water molecules (PC bilayers). As a next step, cholesterol (Chol) molecules were introduced to the PC bilayers (PC-Chol bilayers). These studies provided detailed information about the structure and dynamics of the membrane/water interface and the hydrocarbon chain region in bilayers built of various types of PCs and Chol. This enabled studies of membrane systems of higher complexity. They included the investigation of an integral membrane protein in its natural environment of a PC bilayer, and the antibacterial activity of magainin-2. The latter study req...
Molecular dynamics simulation of the partitioning of benzocaine and phenytoin into a lipid bilayer
Molecular dynamics simulations were used to examine the partitioning behaviour of the local anaesthetic benzocaine and the anti-epileptic phenytoin into lipid bilayers, a factor that is critical to their mode of action. Free energy methods are used to quantify the thermodynamics of drug movement between water and octanol as well as for permeation across a POPC membrane. Both drugs are shown to favourably partition into the lipid bilayer from water and are likely to accumulate just inside the lipid headgroups where they may alter bilayer properties or interact with target proteins. Phenytoin experiences a large barrier to cross the centre of the bilayer due to less favourable energetic interactions in this less dense region of the bilayer. Remarkably, in our simulations both drugs are able to pull water into the bilayer, creating water chains that extend back to bulk, and which may modify the local bilayer properties. We find that the choice of atomic partial charges can have a significant impact on the quantitative results, meaning that careful validation of parameters for new drugs, such as performed here, should be performed prior to their use in biomolecular simulations.
Archives of Biochemistry and Biophysics, 1996
2-chlorethyl)ureas (CEU) 2 (1-3). These molecules are We have investigated the interaction between a new hybrid designed from the unnitrosated pharmacophoric antineoplastic drug, 4-tert-butyl-[3-(2-chloroethyl)ureido] moiety of nitrosoureas and the ''prosthetic'' group of benzene (tBCEU), and distearoylphosphatidylcholine aromatic nitrogen mustards . The effects of difbilayers using differential scanning calorimetry, Fouferent CEU on model membrane are strongly depenrier transform infrared spectroscopy (FT-IR), and dent on the R substituent and are related to the cytohigh-pressure infrared spectroscopy. The results obtoxicity of the drug (4). Therefore, the interactions betained with the three different techniques indicate tween the CEU molecules and the plasma membrane that the drug incorporates in the lipid bilayer. More are potentially important in their mechanism of action. specifically, the incorporation of the tBCEU results in In the present study, we have chosen to investigate in a decrease in the phase transition temperature of the detail the effect of one of the most cytotoxic CEU, 4lipid and in an increase in the amount of gauche contert-butyl-[3-(2-chloroethyl) ureido] benzene (tBCEU), formers in the liquid-crystalline phase. In the gel with model membranes made of 1,2-distearoyl-sn-glycphase, high-pressure FT-IR results indicate that the ero-3-phosphocholine (DSPC) with three different techincorporation of tBCEU decreases the acyl chain packniques. These interactions were studied using differening. In addition, the results suggest the presence of tial scanning calorimetry (DSC), Fourier transform inhydrogen bonding between the lipid carbonyl group frared spectroscopy (FT-IR), and high-pressure FT-IR.
Chemistry and Physics of Lipids, 2006
Differential scanning calorimetry (DSC) has been employed to investigate the thermal changes caused by the anticancer alkaloid drug vinorelbine in dipalmytoylphosphatidylcholine (DPPC) bilayers. The total enthalpy change was increased by the presence of the drug molecule, indicating a partial interdigitation of the lipid alkyl chains. The presence of cholesterol in DPPC bilayers including vinorelbine induced an obstruction of the interdigitation, since cholesterol interrupts the upraise of enthalpy change. Vinorelbine's interdigitation ability and stabilizing properties with the active site of the receptor have been compared with those of similar in structure amphipathic and bulky alkaloid vinblastine. The obtained results may in part explain their similar mechanism of action but different bioactivity.
Journal of Chemical Theory and Computation, 2010
Molecular dynamics simulations of fully hydrated pure bilayers of four widely studied phospholipids, 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and 2-oleoyl-1palmitoyl-sn-glycero-3-phosphocholine (POPC) using a recent revision of the GROMOS96 force field are reported. It is shown that the force field reproduces the structure and the hydration of bilayers formed by each of the four lipids with high accuracy. Specifically, the solvation and the orientation of the dipole of the phosphocholine headgroup and of the ester carbonyls show that the structure of the primary hydration shell in the simulations closely matches experimental findings. This work highlights the need to reproduce a broad range of properties beyond the area per lipid, which is poorly defined experimentally, and to consider the effect of system size and sampling times well beyond those commonly used.
Alamethicin in lipid bilayers: Combined use of X-ray scattering and MD simulations
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2009
We study fully hydrated bilayers of two di-monounsaturated phospholipids diC18:1PC (DOPC) and diC22:1PC with varying amounts of alamethicin (Alm). We combine the use of X-ray diffuse scattering and molecular dynamics simulations to determine the orientation of alamethicin in model lipids. Comparison of the experimental and simulated form factors shows that Alm helices are inserted transmembrane at high humidity and high concentrations, in agreement with earlier results. The x-ray scattering data and the MD simulations agree that membrane thickness changes very little up to 1/10 Alm/DOPC. In contrast, the x-ray data indicate that the thicker diC22:1PC membrane, thins with added Alm, a total decrease in thickness of 4 Å at 1/10 Alm/diC22:1PC. The different effect of Alm on the thickness changes of the two bilayers is consistent with Alm having a hydrophobic thickness close to the hydrophobic thickness of 27 Å for DOPC; Alm is then mismatched with the 7 Å thicker diC22:1PC bilayer. The x-ray data indicate that Alm decreases the bending modulus (K C ) by a factor of ~2 in DOPC and a factor of ~10 in diC22:1PC membranes(P/L ~1/10). The van der Waals and fluctuational interactions between bilayers are also evaluated through determination of the anisotropic B compressibility modulus.
Molecular dynamic simulation study of cholesterol and conjugated double bonds in lipid bilayers
Chemistry and Physics of Lipids, 2011
Conjugated linoleic acids (CLA) are found naturally in dairy products. Two isomers of CLA, that differ only in the location of cis and trans double bonds, are found to have distinct and different biological effects. The cis 9 trans 11 (C9T11) isomer is believed to have anti-carcinogenic effects, while the trans 10 cis 12 (T10C12) isomer is believed to be associated with anti-obesity effects. In this paper we extend earlier Molecular Dynamics (MD) simulations of pure CLAphosphatidylcholine bilayers to investigate the comparative effects of cholesterol on bilayers composed of the two respective isomers. Simulations of phosphatidylcholine lipid bilayers in which the sn-2 chains contained one of the two isomers of CLA were performed in which, for each isomer, the simulated bilayers contained 10%, and 30% cholesterol (Chol). From MD trajectories we calculate and compare structural properties of the bilayers, including areas per molecule, thickness of bilayers, tilt angle of cholesterols, order parameter profiles, and one and twodimensional radial distribution function (RDF), as functions of Chol concentration. While the structural effect of cholesterol is approximately the same for both isomers, we find differences at an atomistic level in order parameter profiles and in two-dimensional radial distribution functions.