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We use all-atom molecular dynamics simulations to extract ΔGeff, the free energy of binding of potassium ions K+ to the partially charged polyelectrolyte poly(acrylic acid), or PAA, in dilute regimes. Upon increasing the charge fraction of PAA, the chains adopt more extended conformations, and simultaneously, potassium ions bind more strongly (i.e., with more negative ΔGeff) to the highly charged chains to relieve electrostatic repulsions between charged monomers along the chains. We compare the simulation results with the predictions of a model that describes potassium binding to PAA chains as a reversible reaction whose binding free energy (ΔGeff) is adjusted from its intrinsic value (ΔG) by electrostatic correlations, captured by a random phase approximation. The bare or intrinsic binding free energy ΔG, which is an input in the model, depends on the binding species and is obtained from the radial distribution function of K+ around the charged monomer of a singly charged, short PAA chain in dilute solutions. We find that the model yields semi-quantitative predictions for ΔGeff and the degree of potassium binding to PAA chains, α, as a function of PAA charge fraction without using fitting parameters. [ABSTRACT FROM AUTHOR]

After reviewing and organizing the literature on the problem of inertial cross-stream migration of rigid spheres in various geometries including tubes and channels, we use Dissipative Particle Dynamics (DPD) simulations to study the simplest case of migration of a single neutrally or non-neutrally buoyant sphere with diameter 20% of the gap in plane Poiseuille flow and assess the potential and limitations of DPD simulations for this and similar problems. We find that the neutrally buoyant sphere lags by up to 6% behind the surrounding fluid and is focused at a position around 50% of the distance between the channel center and the wall. With Re increasing from around 100 to 500, the sphere migrates closer to the channel center. With flow driven by gravity, a much denser non-neutrally buoyant sphere leads the surrounding fluid and is focused at a position closer to the wall, around 60% the distance from the channel center to the wall, in qualitative agreement with previous work. The lower values of the Schmidt number Sc in DPD simulations relative to real fluids, due to the relatively large diffusivity of DPD beads, are shown to not significantly affect the consistency of our DPD results with literature results although they make results noisy at low Re (i.e., ≲ 50). However, the increase in Ma and Wi with increasing Re leads to compressible flow effects and in some cases viscoelastic effects at high Re depending on the DPD parameters chosen. Even for optimally chosen parameters, we require Re ≲ 500 to avoid strong compressibility effects. Thus, the relative simplicity of the DPD method for complex fluid flows is offset by the need to control the effects of unphysically high values of other parameters, such as Ma and Wi, which seriously limits the range of conditions under which DPD simulations give valid results in fluid transport problems. [ABSTRACT FROM AUTHOR]

To understand the origin of transmembrane potentials, formation of transient pores, and the movement of anions and cations across lipid membranes, we have performed systematic atomistic molecular dynamics simulations of palmitoyl-oleoyl-phosphatidylcholine (POPC) lipids. A double bilayer setup was employed and different transmembrane potentials were generated by varying the anion (Cl-) and cation (Na+) concentrations in the two water compartments. A transmembrane potential of ∼350 mV was thereby generated per bilayer for a unit charge imbalance. For transmembrane potential differences of up to ∼1.4 V, the bilayers were stable, over the time scale of the simulations (10–50 ns). At larger imposed potential differences, one of the two bilayers breaks down through formation of a water pore, leading to both anion and cation translocations through the pore. The anions typically have a short residence time inside the pore, while the cations show a wider range of residence times depending on whether they bind to a lipid molecule or not. Over the time scale of the simulations, we do not observe the discharge of the entire potential difference, nor do we observe pore closing, although we observe that the size of the pore decreases as more ions translocate. We also observed a rare lipid flip-flop, in which a lipid molecule translocated from one bilayer leaflet to the opposite leaflet, assisted by the water pore. [ABSTRACT FROM AUTHOR]

We estimate the binding free energy between peptides and an MHC class II molecule using molecular dynamics (MD) simulations with the weighted histogram analysis method (WHAM). We show that, owing to its more thorough sampling in the available computational time, the binding free energy obtained by pulling the whole peptide using a coarse-grained (CG) force field (MARTINI) is less prone to significant error induced by inadequate-sampling than using an atomistic force field (AMBER). We further demonstrate that using CG MD to pull 3-4 residue peptide segments while leaving the remaining peptide segments in the binding groove and adding up the binding free energies of all peptide segments gives robust binding free energy estimations, which are in good agreement with the experimentally measured binding affinities for the peptide sequences studied. Our approach thus provides a promising and computationally efficient way to rapidly and reliably estimate the binding free energy between an arbitrary peptide and an MHC class II molecule. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Into an extended Voorn-Overbeek (EVO) free energy model of polyelectrolyte (PE) complexation and phase behavior, we incorporate three classes of short-ranged electrostatic effects, namely counterion association-dissociation, cross-chain ion pairing (IP), and charge regulation by treating each as a reversible chemical reaction leading to a corresponding law of mass action in a self-consistent fashion. The importance of each reaction is controlled by a corresponding chemistry-dependent standard free energy input parameter. Our model also accounts for Born (or ion solvation) energy using a linear mixing rule for the effective dielectric constant. In monophasic systems, the proposed model can qualitatively explain the observed shifts in acidity and basicity observed in potentiometric titration of weak PEs in the presence of salt and oppositely charged PEs in accordance with Le Châtelier's principle. We demonstrate how a competition between counterion condensation (CC) and IP alone can explain the complex coacervation of strongly charged PEs as well as the existence of a critical salt concentration. Binodal diagrams predicted in our model are also affected by long-ranged electrostatics and are most sensitive to IP strength both for weak and strong PEs. The extent of IP increases in the dense phase at the expense of reduced CC upon coacervation consistent with counter release view of complex coacervation. We compare binodal diagrams predicted by our model against experimental data for both weakly and strongly dissociating polyions pairs and find a plausible parameter set that leads to an acceptable and partial agreement with experiments in the two cases, respectively. [ABSTRACT FROM AUTHOR]

Architectural coatings/paints play a very important role in our world, making our houses and workplaces beautiful, comfortable, and energy-efficient. Polymeric components of coating formulations include latex or binder, dispersants, and thickeners or rheology modifiers [RM]). This review is devoted to the RMs, primarily associative thickeners [AT], specifically highlighting the relationship between the thickener molecular structure, paint formulation, rheology, and application. We briefly describe the chemistries of various associative thickeners ("hydrophobic alkali-swellable emulsion" [HASE], hydrophobically modified hydroxyethylcellulose [HMHEC], and "hydrophobically modified ethoxylated urethane" [HEUR]) polymers. Concentrating on the HEUR thickeners, we then review the structure and rheology of their aqueous solutions and of model paints containing HEURs and latex particles in water. For model paints, we review experimental studies (rheology, NMR, and SANS) and theoretical models from molecular-level classical Molecular Dynamics [MD] to mesoscale coarse-grained MD to large-scale rheology calculations. Lastly, influence of rheological metrics on specific paint application features (flow and leveling, sag resistance, and brush drug) is discussed. We conclude by highlighting opportunities and challenges for future research. [Display omitted] [ABSTRACT FROM AUTHOR]

Weperform coarse-grained molecular dynamics simulations for sodiumdodecyl sulfate (SDS) surfactant using a modification of the Dry Martiniforce field (Arnarez et al. 2014) with implicit water. After inclusionof particle mesh Ewald (PME) electrostatics, an artificially highdielectric constant for water (εr= 150), and reparameterization,we obtain structural and thermodynamic properties of SDS micellesthat are close to those obtained from the standard Martini force fieldwith explicit water, which in turn match those of atomistic simulations.The gains in computational efficiency obtained by removing explicitwater allow direct simulations of the self-assembly of SDS in solution.We observe surfactant exchange among micelles and micelle fissionand fusion and obtain realistic, equilibrated micelle size distributionsat modest computational cost, as well as a transition to cylindricalmicelles at high surfactant concentration or with added salt. We furtherapply this parametrized force field to study the adsorption of SDSonto hydrophobic surfaces and calculate the adsorption kinetics andequilibrium adsorption isotherm. The greatly increased speed of computationof surfactant self-assembly made possible by this Dry Martini methodshould allow future simulation of competitive adsorption of multiplesurfactant species to surfaces, as well as simulation of micellarshape transitions. [ABSTRACT FROM AUTHOR]

Abstract: To explore the role of lung surfactant proteins SP-B and SP-C in storing and redelivering lipid from lipid monolayers during the compression and re-expansion occurring in lungs during breathing, we simulate the folding of lipid monolayers with and without these proteins. We utilize the MARTINI coarse-grained force field to simulate monolayers containing pure dipalmitoylphosphatidylcholine (DPPC) and DPPC mixed with palmitoyloleoylphosphatidylglycerol (POPG), palmitic acid (PA), and/or peptides. The peptides considered include the 25-residue N-terminal fragment of SP-B (SP-B1 – 25), SP-C, and several SP-B1 – 25 mutants in which charged and hydrophilic residues are replaced by hydrophobic ones, or vice-versa. We observe two folding mechanisms: folding by the amplification of undulations and folding by nucleation about a defect. The first mechanism is observed in monolayers containing either POPG or peptides, while the second mechanism is observed only with peptides present, and involves the lipid-mediated aggregation of the peptides into a defect, from which the fold can nucleate. Fold nucleation from a defect displays a dependence on the hydrophobic character of the peptides; if the number of hydrophobic residues is decreased significantly, monolayer folding does not occur. The addition of POPG or peptides to the DPPC monolayer has a fluidizing effect, which assists monolayer folding. In contrast, the addition of PA has a charge-dependent condensing affect on DPPC monolayers containing SP-C. The peptides appear to play a significant role in the folding process, and provide a larger driving force for folding than POPG. In addition to promoting fold formation, the peptides also display fusogenic behavior, which can lead to surface refining. [ABSTRACT FROM AUTHOR]

Despite the success of the mean-field tube theory in predicting the stress relaxation of linear and branched polymers, several important issues remain unresolved. Recent simulation methods that address some of these issues are shedding light on the dynamics of entangled polymer molecules. In this survey, we consider a class of coarse-grained models for polymer melts called slip-link models, which have been used to study the phenomena of constraint release, branch-point diffusion, and the relationship between the plateau modulus and entanglement spacing. We also consider the bond-fluctuation lattice model, and the pearl-necklace molecular dynamics model in conjunction with recently developed algorithms to identify primitive paths. The ability of these latter models to identify the primitive path network enables molecular simulations to be used to test and improve mean-field tube models. The implications of these simulations for the mean-field tube potential in the absence of constraint release, and for the dilution exponent which controls the strength of constraint release, are examined. [ABSTRACT FROM AUTHOR]

We have performed molecular dynamics simulations of the interactions of two α-helical anti-microbial peptides, magainin2 and its synthetic analog of MSI-78, with palmitoyl-oleoyl-phosphatidylcholine (POPC) lipid bilayers. We used various initial positions and orientations of the peptide with respect to the lipid bilayer, including a surface-bound state parallel to the interface, a trans-membrane state, and a partially inserted state. Our 20ns long simulations show that both magainin2 and MSI-78 are most stable in the lipid environment, with the peptide destabilized to different extents in both aqueous and lipid/water interfacial environments. We found that there are strong specific interactions between the lysine residues of the peptides and the lipid head-group regions. MSI-78, owing to its large number of lysines, shows better binding characteristics and overall stability when compared to magainin2. We also find that both peptides destabilize the bilayer environment, as observed by the increase in lipid tail disorder and the induction of local curvature on the lipid head-groups by the peptides. From all the simulations, we conclude that the hydrogen bonding interactions between the lysines of the peptides and the oxygens of the polar lipid head-groups are the strongest and determine the overall peptide binding characteristics to the lipids. [Copyright &y& Elsevier]

[Display omitted] The free energies associated with adsorption/desorption of individual surfactants from micelles and the fusion/scission of long micelles can be used to estimate the rate constants for micellar kinetics as functions of surfactant and salt concentration. We compute the escape free energies △G esc of surfactant from micelles and the scission free energies △G sciss of long micelles from coarse-grained molecular dynamics simulations coupled with umbrella sampling, for micelles of both sodium dodecylsulfate (SDS) in sodium chloride (NaCl) and cetyltrimethylammonium chloride (CTAC) in sodium salicylate (NaSal). For spherical micelles, △G esc values have maxima at certain aggregation numbers, and at salt-to-surfactant molar concentration ratios R near unity, consistent with experiments. For cylindrical micelles, SDS/NaCl shows a minimum, and CTAC/NaSal a maximum in △G esc , both at R ~ 0.7, while △G sciss of CTAC micelles also peaks at around R ~ 0.7 and that of SDS micelles increases monotonically with R. We explain the non-monotonic dependence of escape and scission free energies on R by a combination of electrostatic screening and the decrease of micelle radius with increasing R. Transitions from predominantly spherical to cylindrical micelles, and between adsorption/desorption and fusion/scission kinetics with changing salt concentration can be inferred from the free energies for CTAC/NaSal. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract The influence of a poly(vinyl alcohol) (PVA) molecule on the air/water interfacial structure of adsorbed sodium lauryl ether sulfate with one polyethylene oxide group (SLE1S) was investigated using molecular dynamics simulations. Increasing SLE1S surface density increases the interface thickness and forces both SLE1S and PVA molecules to migrate towards the air (actually vacuum) to different degrees. While most surfactants, when dilute, align parallel with the interface, increasing surfactant surface density forces tail groups gradually to align more perpendicularly to the interface. The three types of oxygen atoms in the SLE1S head group, i.e. the ionic, ester and ether oxygen atoms, form three distinct hydration shells, with PVA monomers appearing both within these shells and between the second and third shell due to its own hydrogen bonding with water and excluded volume of surfactant and water. The ionic oxygen atoms form more hydrogen bonds with water molecules and PVA than do the ester and ether oxygen atoms. The addition of PVA decreases slightly the number of hydrogen bonds between the surfactant oxygen atoms and the water molecules, as PVA chains form new hydrogen bonds with both of them. With increasing surfactant concentration, the PVA is pushed away from the bulk water, decreasing the number of the hydrogen bonds between it and water. These results are relevant to the use of polymers to aid surfactant in aqueous foaming applications. [ABSTRACT FROM AUTHOR]

The article offers a summary of an article within the issue on the nonadditivity of inorganic nanoparticle (NP) interactions. An overview of the molecular dynamic simulations of potential of mean force (PMF), including in regard to their confirming the nonadditivity of van der Waals forces, is provided.

We present a method of modeling nanoparticle (NP) hydrophobicity using coarse-grained molecular dynamics (CG MD) simulations, and apply this to the interaction of lipids with nanoparticles. To model at a coarse-grained level the wettability or hydrophobicity of a given material, we choose the MARTINI coarse-grained force field, and determine through simulation the contact angles of MARTINI water droplets residing on flat regular surfaces composed of various MARTINI bead types (C1, C2, etc.). Each surface is composed of a single bead type in each of three crystallographic symmetries (FCC, BCC, and HCP). While this method lumps together several atoms (for example, one cerium and two oxygens of CeO2) into a single CG bead, we can still capture the overall hydrophobicity of the actual material by choosing the MARTINI bead type that gives the best fit of the contact angle to that of the actual material, as determined by either experimental or all-atom simulations. For different MARTINI bead types, the macroscopic contact angle is obtained by extrapolating the microscopic contact angles of droplets of eight different sizes (containing Nw = 3224-22978 water molecules) to infinite droplet size. For each droplet, the contact angle was computed from a best fit of a circular curve to the droplet interface extrapolated to the first layer of the surface. We then examine how small nanoparticles of differing wettability interact with MARTINI dipalmitoylphosphotidylcholine (DPPC) lipids and SP-C peptides (a component of lung surfactant). The DPPC shows a transition from tails coating the nanoparticle to a hemimicelle coating the water-wet NP, as the contact angle of a water droplet on the surface is lowered below ∼60°. The results are relevant to developing a taxonomy describing the potential nanotoxicity of nanoparticle interactions with components in the lung. [ABSTRACT FROM AUTHOR]

Wecalculate potentials of mean force (PMFs) and mean first passagetimes for a surfactant to escape a micelle, for both ionic sodiumdodecyl sulfate (SDS) and nonionic ethoxylated alcohol (C12E5) micellesusing both atomistic and coarse-grained molecular dynamics (MD) simulations.The PMFs are obtained by umbrella sampling and used in a Smoluchowskifirst-passage-time theory to obtain the times for a surfactant toescape a micelle. The calculated mean first passage time for an SDSmolecule to break away from a micelle (with an aggregation numberof 60) is around 2 μs, which is consistent with previous experimentalmeasurements of the “fast relaxation time” for exchangeof surfactants between the micellar phase and the bulk solvent. Thecorresponding escape time calculated for a nonionic ethoxylated alcoholC12E5, with the same tail length as SDS, is 60 μs, which issignificantly longer than for SDS primarily because the PMF for surfactantdesorption is about 3kT smaller than for C12E5. We also show thattwo coarse-grained (CG) force fields, MARTINI and SDK, give predictionssimilar to the atomistic CHARMM force field for the nonionic C12E5surfactant, but for the ionic SDS surfactant, the CG simulations givea PMF similar to that obtained with CHARMM only if long-range electrostaticinteractions are included in the CG simulations, rather than usinga shifted truncated electrostatic interaction. We also calculate thatthe mean first passage time for an SDS and a C12E5 to escape froma latex binder surface is of the order of milliseconds, which is morethan 100 times longer than the time for escape from the micelle, indicatingthat in latex waterborne coatings, SDS and C12E5 surfactants likelybind preferentially to the latex polymer interface rather than formmicelles, at least at low surfactant concentrations. [ABSTRACT FROM AUTHOR]

Weadopt atomistic molecular dynamics (MD) simulations to studythe solvation and gelation behavior of homogeneous methylcellulose(MC) and model random oligomers that represent the commercial cellulosicpolymer product METHOCEL A in water and acetone solvents. We demonstratethat the two carbohydrate-specific GROMOS force fields, GROMOS 45A4and 56Acarbo, are capable of reproducing characteristic angle distributionsand the persistence length of MC chains reported in the literature.We then use the GROMOS 56Acarbo force field in both single-chain andmultiple-chain simulations to characterize their solvation behaviorthrough radial distribution functions, hydrogen-bond counts, and contactmap analyses. We find that the un-methylated O6 position on the cellulosering forms the most hydrogen bonds, followed by O2 and O3, implyingthat methylation at the 6 position reduces hydrogen bonding more thandoes methylation at other positions. O6–O6 is the most probableintermolecular hydrogen bond between different MC molecules. Dimethylatedand trimethylated MCs form aggregated structures at low temperaturesand precipitate-like structures at high temperatures in water butdisperse randomly in acetone. This is consistent with experimentalobservations of gelation at elevated temperatures in water. The heterogeneousMETHOCEL A model shows increased aggregation of trimethylated monomerunits at elevated temperatures, suggesting that hydrophobic interactionis the main factor that induces the gelation, rather than hydrogenbonding. [ABSTRACT FROM AUTHOR]

We build a united atom model forTween 80 (polyoxyethylene sorbitanoleates), based on the GROMOS53A6OXY+Dforce field, andapply it to two stereoisomers, three constitutional isomers, and threestructures with one, two, and three tails, to represent componentsin the Tween 80 commercial mixture. In a preassembled micelle containing60 molecules, the distribution of Tween tail and ethylene oxide headgroups is found to be insensitive to stereoisomerization but sensitiveto changes in relative lengths of the four polyoxyethylene head groups.At the air–water and oil–water interfaces, the interfacialtension is significantly lower for the constitutional isomer witha shorter W headgroup, which attaches the tail to the sorbitan ring,and for Tween 80 isomers with more than one tail group. The resultsindicate the possible scope for improvement in the design of polyoxyethylenesorbitan oleates with improved surface tension reduction or betterspreading at the oil–water interface. We also report surfactantcomponent distribution profiles within preassembled micelles and atinterfaces that can be used for validating coarse-grained surfactantmodels needed for simulation of self-assembly of Tween 80 surfactantmixtures. [ABSTRACT FROM AUTHOR]

Moleculardynamic (MD) simulations of preassembled sodium dodecylsulfate (SDS) micelles are carried out using three versions of GROMOS,as well as CHARMM36, OPLS-AA, and OPLS-UA force fields at differentaggregation numbers and box sizes. The differences among force fieldshave little effect on the overall micelle structure of small aggregatesof size 60 or 100, but for micelles of an aggregation number of 300or higher, bicelle structures with ordered tails, rather than themore realistic rodlike or cylindrical micelles with disordered tails,occur when using versions of GROMOS45A3 or the OPLS-AA force fieldsthat are adapted to model the sulfate head group atoms using methodsgiven in the literature. We find that the Lennard-Jones (L-J) parametersfor the sodium ions and the ionic oxygens of the SDS head group, aswell as the water model, control the transition to bicelles, regardlessof other L-J parameters. A closer binding of the sodium ions to thehead group ionic oxygens screens the electrostatic repulsions morestrongly, resulting in condensation of SDS head groups, leading tounphysical bicelles for GROMOS45A3 or the OPLS-AA force fields, whenthe aggregation number is large. A telltale sign that the sodium–oxygeninteraction is too strong shows up in high nearest neighbor peaks(height >8 and height >20 for micelles with 60 and 100 surfactants,respectively) in the radial distribution functions (RDFs) of sodiumions to ionic oxygens. In the 100-surfactant micelles, the high RDFpeak is accompanied by “crystal-like” layering of sodiumions onto the surface of the micelle. The distance between the sodiumions and micelle also depends on the number of waters binding to sodiumions in the presence of surfactant head groups, which depends on boththe sodium ion and water models, and for the same sodium model increasesas the water model is changed in the order: TIP4P, SPC/E, SPC, andTIP3P. [ABSTRACT FROM AUTHOR]

We performed all-atom and coarse-grained (CG) moleculardynamics (MD) simulations of lipid bilayers grafted with elastin-likepolypeptides (ELPs; [VPGVG]n). All-atomsimulations of a single ELP in water show that ELPs become more collapsedand folded as the temperature increases from 293 up to 353 K, in agreementwith experiments. All-atom simulations of lipid bilayers composedof dipalmitoylglycerophosphocholine (DPPC), cholesterol, and fattyacids grafted with ELPs show that ELPs insert into the bilayer andsignificantly disorder lipids, to an extent that depends on the ELPlength over the temperature range 293–323 K. In the bilayer,ELPs are mainly, but not entirely, random coil in character at temperaturesbetween 293 and 315 K and, in contrast to the behavior in water, becomeincreasing random coil and extended in length over the range 315–323K, over which the bilayer is in the disordered liquid phase. The insertionof ELPs into the lipid-tail region is mediated by the interactionof hydrophobic Pro and Val residues with lipid tails, which becomestronger at increased temperature, but the insertion is incompletebecause of the interaction between hydrophilic backbones of Gly residuesand the lipid headgroups. Longer time CG simulations of the transitionfrom ordered gel to disordered liquid bilayer at 315 K in a liposomeare able to capture cholesterol flip-flops between bilayer leaflets,leading to an increase in the number of cholesterols in the innerlayer, which helps the bilayer accommodate the reduced membrane curvatureresulting from the expansion of the bilayer area driven by the phasetransition. Our findings indicate that lipid bilayers can be disruptedmore effectively by the stronger hydrophobic interaction of the randomcoils of ELPs at 315–323 K than by the compact ELPs at 293–310K, which helps explain the experimental observation that ELP-conjugatedliposomes are stable at 310 K, but become unstable and release drugsat 315 K. [ABSTRACT FROM AUTHOR]

We present molecular dynamics (MD) and slip-springs modelsimulationsof the chain segmental dynamics in entangled linear polymer melts.The time-dependent behavior of the segmental orientation autocorrelationfunctions and mean-square segmental displacements are analyzed forboth flexible and semiflexible chains, with particular attention paidto the scaling relations among these dynamic quantities. Effectivecombination of the two simulation methods at different coarse-graininglevels allows us to explore the chain dynamics for chain lengths rangingfrom Z≈ 2 to 90 entanglements. For a givenchain length of Z≈ 15, the time scales accessedspan for more than 10 decades, covering all of the interesting relaxationregimes. The obtained time dependence of the monomer mean square displacements, g1(t), is in good agreementwith the tube theory predictions. Results on the first- and second-ordersegmental orientation autocorrelation functions, C1(t) and C2(t), demonstrate a clear power law relationshipof C2(t) ∼ C1(t)mwith m= 3, 2, and 1 in the initial, freeRouse, and entangled (constrained Rouse) regimes, respectively. Thereturn-to-origin hypothesis, which leads to inverse proportionalitybetween the segmental orientation autocorrelation functions and g1(t) in the entangled regime,is convincingly verified by the simulation result of C1(t) ∝ g1(t)−1∝ t–1/4in the constrained Rouse regime,where for well-entangled chains both C1(t) and g1(t) are rather insensitive to the constraint release effects. However,the second-order correlation function, C2(t), shows much stronger sensitivity to the constraintrelease effects and experiences a protracted crossover from the freeRouse to entangled regime. This crossover region extends for at leastone decade in time longer than that of C1(t). The predicted time scaling behavior of C2(t) ∝ t–1/4is observed in slip-springs simulations onlyat chain length of 90 entanglements, whereas shorter chains show higherscaling exponents. The reported simulation work can be applied tounderstand the observations of the NMR experiments. [ABSTRACT FROM AUTHOR]

Abstract: To explore the role of individual lung surfactant components in liquid-condensed (LC)/liquid-expanded (LE) phase transitions the MARTINI coarse-grained (CG) model is used to simulate monolayers containing DPPC and additional lipid or peptide components. Our analysis suggests that the LC phase forms from the LE phase via a nucleation and growth mechanism, while the LC–LE transition occurs by melting that originates from defects in the monolayer. On the time scale of our simulations, DPPC monolayers display a substantial hysteresis between the ordering and disordering transitions, which is decreased by the addition of a second component. In binary mixtures of DPPC with lung surfactant peptide fragment SP-B1–25, the ordered side of the hysteresis loop is abolished altogether, suggesting that SP-B1–25 effectively nucleates disorder in the monolayer on heating. SP-B1–25 is observed to perturb the packing of the surrounding lipids leading to local fluidization of the monolayer and to aggregate within the LE phase. In 1:1 DPPC:POPC monolayers, a high concentration of unsaturated phospholipid leads to a substantial decrease in the LC–LE and LE–LC transition temperatures. Adding cholesterol to pure DPPC increases the LC–LE and LE–LC transition temperatures and increases the order on the disordered side of the hysteresis loop leading to a phase of intermediate order, which could be the liquid-disordered (Ld) phase. Cholesterol is also observed to show a preference for LC–LE domain boundaries. The results of our molecular dynamics simulations coincide with many experimental observations and can help provide insight into the physiological roles of individual surfactant components. [Copyright &y& Elsevier]

Using coarse-grained molecular dynamics simulations and an umbrella sampling method that uses local surfactant density as a reaction coordinate, we directly calculate, for the first time, both the scission and branching free energies of a model charged micelle [cationic cetyltrimethylammonium chloride (CTAC)] in the presence of inorganic and organic salts (hydrotropes). We find that while inorganic salt only weakly affects the micelle scission energy, organic hydrotropes produce a strong, nonmonotonic dependence of both scission energy and branching on salt concentration. The nonmonotonicity in scission energy is traced to a competition between electrostatic screening of the repulsions among the surfactant head groups and thinning of the micellar core, which result from attachment of the hydrotropes to the micelle surface. We are able to correlate the nonmonotonicity in the scission energy of CTAC micelles with the peak observed experimentally in viscosity versus hydrotrope concentration and the location of this peak in CTAC solutions. [ABSTRACT FROM AUTHOR]

Heparindecomplexation experiments, as well as all-atom (AA) andcoarse-grained (CG) molecular dynamics (MD) simulations, were performedto determine the effect of the size of arginine(Arg)-rich peptideson the structure and binding strength of the siRNA–peptidecomplex. At a fixed peptide/siRNA mole ratio of 5:1 or 10:1, the siRNAcomplexes with peptides longer than nine Arg residues are more easilydecomplexed by heparin than are those with nine Arg residues. At thesemole ratios, peptides longer than nine Arg residues have cationic/anioniccharge ratios in excess of unity, and produce more weakly bound complexesthan nine Arg residue ones do. AA simulations of mixtures of peptideswith a single siRNA show formation of an electrostatically inducedcomplex, and the longer peptides produce a larger complex, but withno significant increase in the number of Arg residues bound to thesiRNA. Larger-scale CG-MD simulations show that multiple siRNAs canbe linked together by peptides into a large complex, as observed inthe experiments. The peptides longer than nine residues, which atmole ratio 5:1 yield a peptide/siRNA charge ratio in excess of unity,include many noninteracting Arg residues, which repel each other electrostatically.This leads to a less dense complex than for 9-residue peptides, whichcan explain why these longer complexes are more easily decomplexedby heparin molecules, as observed in the experiments. The key roleof the charge ratio is supported by simulations that show that, ata mole ratio of 2.5 peptides per siRNA, the longer 18-residue peptidehas a charge ratio of roughly unity and also shows a tight complex,just as the 9-residue peptide does at a 5:1 mole ratio, where itscharge ratio is also unity. [ABSTRACT FROM AUTHOR]

Abstract: The second transmembrane (TM2) domain of GABAA receptor forms the inner-lining surface of chloride ion-channel and plays important roles in the function of the receptor protein. In this study, we report the first structure of TM2 in lipid bilayers determined using solid-state NMR and MD simulations. The interatomic 13C–15N distances measured from REDOR magic angle spinning experiments on multilamellar vesicles, containing a TM2 peptide site specifically labeled with 13C′ and 15N isotopes, were used to determine the secondary structure of the peptide. The 15N chemical shift and 1H–15N dipolar coupling parameters measured from PISEMA experiments on mechanically aligned phospholipid bilayers, containing a TM2 peptide site specifically labeled with 15N isotopes, under static conditions were used to determine the membrane orientation of the peptide. Our results reveal that the TM2 peptide forms an alpha helical conformation with a tilted transmembrane orientation, which is unstable as a monomer but stable as pentameric oligomers as indicated by MD simulations. Even though the peptide consists of a number of hydrophilic residues, the transmembrane folding of the peptide is stabilized by intermolecular hydrogen bondings between the side chains of Ser and Thr residues as revealed by MD simulations. The results also suggest that peptide–peptide interactions in the tilted transmembrane orientation overcome the hydrophobic mismatch between the peptide and bilayer thickness. [Copyright &y& Elsevier]

Cell-signaling peptides have been extensively used to transport functional molecules across the plasma membrane into living cells. These peptides consist of a hydrophobic sequence and a cationic nuclear localization sequence (NLS). It has been assumed that the hydrophobic region penetrates the hydrophobic lipid bilayer and delivers the NLS inside the cell. To better understand the transport mechanism of these peptides, in this study, we investigated the structure, orientation, tilt of the peptide relative to the bilayer normal, and the membrane interaction of two cell-signaling peptides, SA and SKP. Results from CD and solid-state NMR experiments combined with molecular dynamics simulations suggest that the hydrophobic region is helical and has a transmembrane orientation with the helical axis tilted away from the bilayer normal. The influence of the hydrophobic mismatch, between the hydrophobic length of the peptide and the hydrophobic thickness of the bilayer, on the tilt angle of the peptides was investigated using thicker POPC and thinner DMPC bilayers. NMR experiments showed that the hydrophobic domain of each peptide has a tilt angle of 15 ± 30 in POPC, whereas in DMPC, 25 ± 30 and 30 ± 30 tilts were observed for SA and SKP peptides, respectively. These results are in good agreement with molecular dynamics simulations, which predict a tilt angle of 13.3° (SA in POPC), 16.4° (SKP in POPC), 22.3° (SA in DMPC), and 31.70 (SKP in DMPC). These results and simulations on the hydrophobic fragment of SA or SKP suggest that the tilt of helices increases with a decrease in bilayer thickness without changing the phase, order, and structure of the lipid bilayers. [ABSTRACT FROM AUTHOR]