Aggregation of modified hexabenzocoronenes as models for early stage asphaltene self-assembly

<p>Molecular dynamics simulations were performed on solvated systems containing three molecules of hexabenzocoronene (HBC) derivatives to model the initial self-association of asphaltenes. Specifically, the hexane-modified HBC (HBC6) and those with substitutions containing a side chain with sulphur at three positions (α-H6SA, β-H6SB, and γ-HBCS) and a nitrogen substitution (H6N1) are included. These molecules were solvated with 20 mol% heptane and 80% toluene. Intermediate aggregation states, partial (two molecule clusters), as well as full aggregation of trimer clusters were observed. The conformation of the associated clusters was characterised by π–π stacking, giving the cluster a pre-rod-like shape. The aggregates displayed stability and did not dissociate throughout the course of the simulation (100–530 ns). In particular, the H6SB system showed statistically significant difference in means for both the separation distance and overall interaction energy. H6N1 and H6SA systems differed from the others in terms of electrostatic contributions. To gain a thorough understanding of initial aggregation behaviour and conditions of asphaltenes, additional simulations need to be conducted, in particular those incorporating oxygen substitutions as oxygen is a common heteroatom in crude.</p

Molecular Dynamics Simulations of Ceramide and Ceramide-Phosphatidylcholine Bilayers

Recent studies in lipid raft formation and stratum corneum permeability have focused on the role of ceramides (CER). In this study, we use the all-atom CHARMM36 (C36) force field to simulate bilayers using <i>N</i>-palmitoylsphingosine (CER16) or α-hydroxy-<i>N</i>-stearoyl phytosphingosine (CER­[AP]) in 1,2-dimyristoyl-<i>sn</i>-glycero-3-phosphocholine (DMPC) or 1-palmitoyl-2-oleoylphosphatidylcholine (POPC), which serve as general membrane models. Conditions are replicated from experimental studies for comparison purposes, and concentration (<i>X</i>_CER) is varied to probe the effect of CER on these systems. Comparisons with experiment based on deuterium order parameters and bilayer thickness demonstrate good agreement, thus supporting further use of the C36 force field. CER concentration is shown to have a profound effect on nearly all membrane properties including surface area per lipid, chain order and tilt, area compressibility moduli, bilayer thickness, hydrogen bonding, and lipid clustering. Hydrogen bonding in particular can significantly affect other membrane properties and can even encourage transition to a gel phase. Despite CER’s tendency to condense the membrane, an expansion of CER lipids with increasing <i>X</i>_CER is possible depending on how the balance between various hydrogen-bond pairs and lipid clustering is perturbed. Based on gel phase transitions, support is given for phytosphingosine’s role as a hydrogen-bond bridge between sphingosine ordered domains in the stratum corneum

The simultaneous mass and energy evaporation (SM2E) model

<p>In this article, the Simultaneous Mass and Energy Evaporation (SM2E) model is presented. The SM2E model is based on theoretical models for mass and energy transfer. The theoretical models systematically under or over predicted at various flow conditions: laminar, transition, and turbulent. These models were harmonized with experimental measurements to eliminate systematic under or over predictions; a total of 113 measured evaporation rates were used. The SM2E model can be used to estimate evaporation rates for pure liquids as well as liquid mixtures at laminar, transition, and turbulent flow conditions. However, due to limited availability of evaporation data, the model has so far only been tested against data for pure liquids and binary mixtures. The model can take evaporative cooling into account and when the temperature of the evaporating liquid or liquid mixture is known (e.g., isothermal evaporation), the SM2E model reduces to a mass transfer-only model.</p

Simulations of Pure Ceramide and Ternary Lipid Mixtures as Simple Interior <i>Stratum Corneum</i> Models

The barrier function of the <i>stratum corneum</i> (SC) is intimately related to the structure of the lipid matrix, which is composed of ceramides (Cer), cholesterol (Chol), and free fatty acid (FFA). In this study, the all-atom CHARMM36 (C36) force field is used to simulate bilayers of <i>N</i>-palmitoylsphingosine (Cer16), <i>N</i>-lignoceroylsphingosine (Cer24), Chol, and lignoceric acid (LA) as simple models of the SC. Equimolar mixtures of Cer, Chol, and LA are replicated from experiment for comparison and validation of the C36 force field, and the effects of lipid diversity and temperature are studied. The presence of Chol and LA have effects on nearly all membrane properties including surface area per lipid, area compressibility moduli, chain order, Chol tilt, bilayer thickness, interdigitation, hydrogen bonding, and lipid clustering, while temperature has a more moderate effect. In systems containing Cer16, there is a profound difference in interdigitation between pure Cer and mixed systems, while systems containing Cer24 are relatively unaffected. Increasing temperature has the potential to shift hydrogen bonding pairs rather than uniformly decrease bonding, which can lead to greater Cer–Cer bonding at higher temperatures. Comparison with deuterium order parameter experiments demonstrates good agreement, which supports further use of this class of lipids and fatty acids for development of more complex SC models

Two sterols, two bilayers: insights on membrane structure from molecular dynamics

<p>Cholesterol (CHL) and ergosterol (ERG) are two predominant sterols in eukaryotic cells. The differences in their chemical structure can influence membrane structure and dynamics; this study discusses the effect CHL and ERG have on yeast membrane models with characteristic lipid composition for the endoplasmic reticulum (ER) and the trans-Golgi network (TGN) of yeast <i>Saccharomyces cerevisiae</i>. Molecular dynamics simulations were used to understand the atomic details of the sterols’ interaction with lipid bilayers that have both saturated and unsaturated tails as well as neutral and charged headgroups. Our models include phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol lipids to mimic the environment of the ER and TGN. The models for each organelle are identical, respectively, except for the sterol type. The overall surface area per lipid has no statistical difference between models for the same organelle, 63.6 ± 0.4 Å² in the ER and 60.9 ± 0.4 Å² in the TGN with either ERG or CHL. However, the compressibility modulus is approximately 30% lower in the models with ERG. We analyse this difference based on the sterols’ chemical structure and examine other membrane properties such as the lipid tails order parameters, bilayer thicknesses, sterol tilt angles and sterol spatial orientation with respect to the lipid tails to compare trends with existing data from simulation as well as experiment. This is the first study, to our knowledge, to examine the effect of sterol type on multi-lipid bilayer models with all-atom molecular dynamics.</p

Modeling Yeast Organelle Membranes and How Lipid Diversity Influences Bilayer Properties

Membrane lipids are important for the health and proper function of cell membranes. We have improved computational membrane models for specific organelles in yeast <i>Saccharomyces cerevisiae</i> to study the effect of lipid diversity on membrane structure and dynamics. Previous molecular dynamics simulations were performed by Jo et al. [(2009) <i>Biophys J.</i> <i>97</i>, 50–58] on yeast membrane models having six lipid types with compositions averaged between the endoplasmic reticulum (ER) and the plasma membrane (PM). We incorporated ergosterol, phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol lipids in our models to better describe the unique composition of the PM, ER, and trans-Golgi network (TGN) bilayers of yeast. Our results describe membrane structure based on order parameters (<i>S</i>_CD), electron density profiles (EDPs), and lipid packing. The average surface area per lipid decreased from 63.8 ± 0.4 Ų in the ER to 47.1 ± 0.3 Ų in the PM, while the compressibility modulus (<i>K</i>_A) varied in the opposite direction. The high <i>S</i>_CD values for the PM lipids indicated a more ordered bilayer core, while the corresponding lipids in the ER and TGN models had lower parameters by a factor of at least 0.7. The hydrophobic core thickness (2<i>D</i>_C) as estimated from EDPs is the thickest for PM, which is in agreement with estimates of hydrophobic regions of transmembrane proteins from the Orientation of Proteins in Membranes database. Our results show the importance of lipid diversity and composition on a bilayer’s structural and mechanical properties, which in turn influences interactions with the proteins and membrane-bound molecules

Update of the Cholesterol Force Field Parameters in CHARMM

A modification of the CHARMM36 lipid force field (C36) for cholesterol, henceforth, called C36c, is reported. A fused ring compound, decalin, was used to model the steroid section of cholesterol. For decalin, C36 inaccurately predicts the heat of vaporization (∼10 kJ/mol) and molar volume (∼10 cc/mol), but C36c resulted in near perfect comparison with experiment. MD simulations of decalin and heptane at various compositions were run to estimate the enthalpy and volumes of mixing to compare to experiment for this simple model of cholesterol in a chain environment. Superior estimates for these thermodynamic properties were obtained with C36c versus C36. These new parameters were applied to cholesterol, and quantum mechanical calculations were performed to modify the torsional potential of an acyl chain torsion for cholesterol. This model was tested through simulations of DMPC/10% cholesterol, DMPC/30% cholesterol, and DOPC/10% cholesterol. The C36 and C36c results were similar for surface areas per lipid, deuterium order parameters, electron density profiles, and atomic form factors and generally agree well with experiment. However, C36 and C36c produced slightly different cholesterol angle distributions with C36c adopting a more perpendicular orientation with respect to the bilayer plane. The new parameters in the C36c modification should enable more accurate simulations of lipid bilayers with cholesterol, especially for those interested in the free energy of lipid flip/flop or transfer of phospholipids and/or cholesterol

Parameterization of the CHARMM All-Atom Force Field for Ether Lipids and Model Linear Ethers

Linear ethers such as polyethylene glycol have extensive industrial and medical applications. Additionally, phospholipids containing an ether linkage between the glycerol backbone and hydrophobic tails are prevalent in human red blood cells and nerve tissue. This study uses ab initio results to revise the CHARMM additive (C36) partial-charge and dihedral parameters for linear ethers and develop parameters for the ether-linked phospholipid 1,2-di-<i>O</i>-hexadecyl-<i>sn</i>-glycero-3-phosphocholine (DHPC). The new force field, called C36e, more accurately represents the dihedral potential energy landscape and improves the densities and free energies of hydration of linear ethers. C36e allows more water to penetrate into a DHPC bilayer, increasing the surface area per lipid compared to simulations carried out with the original C36 ether parameters and improving the overall structural properties obtained from X-ray and neutron scattering. Comparison with an ester-linked DPPC bilayer (1,2-dipalmitoyl-<i>sn</i>-phosphatidylcholine) reveals that the ether linkage increases water organization in the headgroup region. This effect is a likely explanation for the experimentally lower water permeability of bilayers composed of ether-linked lipids