A study of the interaction between cell membranes and small molecules derived from lignin, a protective phenolic biopolymer found in vascular plants, is crucial for identifying their potential as pharmacological and toxicological agents. In this work, the interactions of model cell membranes [supported 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid bilayers] are compared for three βO4 dimers of coniferyl alcohol (G lignin monomer): guaiacylglycerol guaiacol ester with a hydroxypropenyl (HOC3H4-) tail (G-βO4′-G), a truncated GG dimer without HOC3H4- (G-βO4′-truncG), and a benzylated GG dimer (benzG-βO4′-G). The uptake of the lignin dimers (per mass of lipid) and the energy dissipation (a measure of bilayer disorder) are higher for benzG-βO4′-G and G-βO4′-truncG than those for G-βO4′-G in the gel-phase DPPC bilayer, as measured using quartz crystal microbalance with dissipation (QCM-D). A similar uptake of G-βO4′-truncG is observed for a fluid-phase bilayer of 1,2-dioleoyl-sn-glycero-3-phosphocholine, suggesting that the effect of the bilayer phase on dimer uptake is minimal. The effects of increasing lignin dimer concentration are examined through an analysis of density profiles, potential of mean force curves, lipid order parameters, and bilayer area compressibilities (disorder) in the lipid bilayers obtained from molecular dynamics simulations. Dimer distributions and potentials of mean force indicate that the penetration into bilayers is higher for benzG-βO4′-G and G-βO4′-truncG than that for G-βO4′-G, consistent with the QCM-D results. Increased lipid tail disorder due to dimer penetration leads to a thinning and softening of the bilayers. Minor differences in the structure of lignin derivatives (such as truncating the hydroxypropenyl tail) have significant impacts on their ability to penetrate lipid bilayers.
An implementation of the replica exchange with dynamical scaling (REDS) method in the commonly used molecular dynamics program GROMACS is presented. REDS is a replica exchange method that requires fewer replicas than conventional replica exchange while still providing data over a range of temperatures and can be used in either constant volume or constant pressure ensembles. Details for running REDS simulations are given, and an application to the human islet amyloid polypeptide (hIAPP) 11-25 fragment shows that the model efficiently samples conformational space.
Transport of single molecules in nanochannels or nanoslits might be used to identify them via their transit (flight) times. In this paper, we present molecular dynamics simulations of transport of single deoxynucleotide 5′-monophoshates (dNMP) in aqueous solution under pressure-driven flow, to average velocities between 0.4 and 1.0 m/s, in 3 nm wide slits with hydrophobic walls. The simulation results show that, while moving along the slit, the mononucleotides are adsorbed and desorbed from the walls multiple times. For the simulations, the estimated minimum slit length required for separation of the dNMP flight time distributions is about 5.9 μm, and the minimum analysis time per dNMP is about 10 μs. These are determined by the nature of the nucleotide–wall interactions, channel width, and by the flow characteristics. A simple analysis using realistic dNMP velocities shows that, in order to reduce the effects of diffusional broadening and keep the analysis time per dNMP reasonably small, the nucleotide velocity should be relatively high. Tailored surface chemistry could lead to further reduction of the analysis time toward its minimum value for a given driving force.
There is potential for flight time based DNA sequencing involving disassembly into individual nucleotides which would pass through a nanochannel with two or more detectors. We performed molecular dynamics simulations of electrophoretic motion of single DNA nucleotides through 3 nm wide hydrophobic slits with both smooth and rough walls. The electric field (E) varied from 0.0 to 0.6 V/nm. The nucleotides adsorb and desorb from walls multiple times during their transit through the slit. The nucleotide–wall interactions differed due to nucleotide hydrophobicities and wall roughness which determined duration and frequency of nucleotide adsorptions and their velocities while adsorbed. Transient association of nucleotides with one, two, or three sodium ions occurred, but the mean association numbers (ANs) were weak functions of nucleotide type. Nucleotide–wall interactions contributed more to separation of nucleotide flight time distributions than ion association and thus indicate that nucleotide–wall interactions play a defining role in successfully discriminating between nucleotides on the basis of their flight times through nanochannels/slits. With smooth walls, smaller nucleotides moved faster, but with rough walls larger nucleotides moved faster due to fewer favorable wall adsorption sites. This indicates that roughness, or surface patterning, might be exploited to achieve better time-of-flight based discrimination between nucleotides.
SIMtoEXP is a software package designed to facilitate the comparison of biomembrane simulations with experimental X-ray and neutron scattering data. It has the following features: (1) Accepts number density profiles from simulations in a standard but flexible format. (2) Calculates the electron density ε(z) and neutron scattering length density ν(z) profiles along the z direction (i.e., normal to the membrane) and their respective Fourier transforms (i.e., Fε[qz] and Fν[qz]). The resultant four functions are then displayed graphically. (3) Accepts experimental Fε(qz) and Fν(qz) data for graphical comparison with simulations. (4) Allows for lipids and other large molecules to be parsed into component groups by the user and calculates the component volumes following Petrache et al. (Biophys J 72:2237–2242, 1997). The software then calculates and displays the contributions of each component group as volume probability profiles, ρ(z), as well as the contributions of each component to ε(z) and ν(z).
The structural parameters of fluid phase bilayers composed of phosphatidylcholines with fully saturated, mixed, and branched fatty acid chains, at several temperatures, have been determined by simultaneously analyzing small-angle neutron and X-ray scattering data. Bilayer parameters, such as area per lipid and overall bilayer thickness have been obtained in conjunction with intrabilayer structural parameters (e.g. hydrocarbonregion thickness). The results have allowed us to assess the effect of temperature and hydrocarbon chain composition on bilayer structure. For example, we found that for all lipids there is, not surprisingly, an increase in fatty acid chain trans–gauche isomerization with increasing temperature. Moreover, this increase in trans–gauche isomerization scales with fatty acid chain length in mixed chain lipids. However, in the case of lipids with saturated fatty acid chains, trans–gauche isomerization is increasingly tempered by attractive chain–chain van der Waals interactions with increasing chain length. Finally, our results confirm a strong dependence of lipid chain dynamics as a function of double bond position along fatty acid chains.
Following our previous efforts in determining the structures of commonlyused PC, PG, and PS bilayers, we continue our studies of fully hydrated, fluid phase PE bilayers. The newly designed parsing scheme for PE bilayers was based on extensive MD simulations, and is utilized in the SDP analysis of both X-ray and neutron (contrast varied) scattering measurements. Obtained experimental scattering form factors are directly compared to our simulation results, and can serve as a benchmark for future developed force fields. Among the evaluated structural parameters, namely, area per lipid A, overallbilayer thickness DB, and hydrocarbon region thickness 2DC, the PE bilayer response to changing temperature is similar to previously studied bilayers with different headgroups. On the other hand, the reduced hydration of PE headgroups, as well as the strong hydrogen bonding between PE headgroups, dramatically affects lateral packing within the bilayer. Despite sharing the same glycerol backbone, a markedly smaller area per lipid distinguishes PE from other bilayers (i.e., PC, PG, and PS) studied to date. Overall, our data are consistent with the notion that lipid headgroups govern bilayer packing, while hydrocarbon chains dominate the bilayer’s response to temperature changes.