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Abstract Tenebrio molitor antifreeze protein (TmAFP) was simulated with growing ice surfaces such as primary prism, secondary prism, basal, and pyramidal planes. The ice-binding site of TmAFP, which is full of threonine (Thr), binds to the primary-prism plane but does not bind to other ice planes, in agreement with experiments showing the fast adsorption of TmAFP to the primary-prism plane. To mimic the ice-binding site of shorthorn sculpin AFP (ssAFP; type I) that predominantly consists of alanine (Ala) and has the binding affinity to the secondary-prism plane, the ice-binding site of TmAFP was mutated by replacing a few Thr residues with Ala residues, showing that mutated TmAFP binds to the secondary-prism plane, similar to the ice-binding affinity of ssAFP. Ala residues are located at the cavity of ice, while Thr residues form hydrogen bonds with water molecules. When the mutated TmAFP is further modified by removing Thr, it does not bind to the secondary-prism plane. These findings indicate that simulations can successfully capture the experimentally observed binding affinity of AFP to specific ice planes, to an extent dependent on hydrophobicity of the ice-binding site. In particular, the addition of hydrophobic residues influences the ice-binding affinity of TmAFP, while a certain amount of hydrophilic residue is still required for hydrogen-bond interactions, which supports experimental observations regarding the key roles of hydrophobic and hydrophilic interactions on the AFP-ice binding. Graphical abstract Image 1 Highlights • Simulations capture the specific binding affinity of TmAFP to primary-prism plane. • The addition of hydrophobic residues influences the ice-binding affinity of TmAFP. • Ala residues are at the ice cavity, while Thr residues form hydrogen bonds with water. [ABSTRACT FROM AUTHOR]

Single-walled carbon nanotubes (SWCNTs) covalently functionalized or noncovalently coated with polyethylene glycol (PEG) of different sizes (M w = 2000 and 5000) and grafting densities (5–16 PEGs per SWCNT) are simulated with human fibrinogen (HFG) and serum albumin (HSA). Proteins migrate toward the SWCNT, but their adsorption extents differ. The extent of the HFG-SWCNT binding decreases with increasing PEG size and grafting density because PEGs more completely cover SWCNTs and thus block hydrophobic interactions between HFGs and SWCNTs, which occurs on PEG-functionalized SWCNTs but not on PEG-coated ones. In particular, the HFG-SWCNT binding significantly decreases in the transition region of PEG conformation from mushroom to brush, where PEGs extend like brushes as described in the Alexander-de Gennes theory. While the HFG adsorption is modulated by PEG conformation, the HSA adsorption is much weaker and less influenced by PEG, because spherical HSAs can bind to the restricted area of the SWCNT and thus cannot bind to the SWCNT as tightly as do linear HFGs. These findings agree with experiments showing less adsorption of proteins on the SWCNT functionalized with larger and more PEGs, and support experimental suggestions regarding the dependence of protein adsorption on protein shape and the mushroom-brush transition of PEG conformation. [ABSTRACT FROM AUTHOR]

Polyelectrolyte bilayers, which consist of poly- l -lysine (PLL) and hyaluronic acid (HA) were simulated with lipid membranes at different temperatures and ion concentrations. Starting with the sequential deposition of PLL and HA above the membrane surface, PLL and HA become completely mixed, leading to the formation of stable bilayers. PLL/HA bilayers are thicker at higher salt concentration because of weakened electrostatic interactions between PLLs and membrane lipids, in agreement with experiments. This salt effect decreases as PLL size increases. Also, bilayers become thinner at higher temperature because of the increased surface area of membrane. In particular, regardless of temperature and salt concentration, larger PLLs induce thicker bilayers, although larger PLLs have lower diffusivities than do smaller ones. Bilayers with larger PLLs show larger vacancy (more water) inside the bilayer, indicating that larger PLLs are less densely stacked on membrane surface than do smaller ones and thus form the thicker bilayer. These findings show the lower diffusivity of larger polyelectrolytes, which supports the experimental observation regarding the restricted diffusion of large polymers, and also imply the dependence of bilayer thickness on the polymer size. [ABSTRACT FROM AUTHOR]

Gramicidin A (gA) dimers with bilayers, which consist of phospholipids and ionic liquids (ILs) at different molar ratios, were simulated at different salt concentrations of 0.15 and 1 M NaCl. Bilayer thickness is larger than the length of a gA dimer, and hence lipids around the gA dimer are significantly disordered to adapt to the gA dimer, yielding membrane curvature. As the IL concentration increases, the bilayer thickness decreases and becomes closer to the gA length, leading to less membrane curvature. Also, ILs significantly increase lateral diffusivities of the gA dimer and lipids at 0.15 M NaCl, but not at 1 M NaCl because strong electrostatic interactions between salt ions and lipid head groups suppress an increase in the lateral mobility of the bilayer at high salt concentration. These findings help explain the conflicting experimental results that showed the increased ion permeability in electrophysiological experiments at 1 M NaCl, but the reduced ion permeability in fluorescent experiments at 0.15 M NaCl. ILs disorder lipids and make bilayers thinner, which yields less membrane curvature around the gA dimer and thus stabilizes the gA dimer, leading to the increased ion permeability. This IL effect predominantly occurs at 1 M NaCl, where ILs only slightly increase the bilayer dynamics because of the strong electrostatic interactions between salt ions and lipids. In contrast, at 0.15 M NaCl, ILs do not only stabilize the curved bilayer but also significantly increase the lateral mobility of gA dimers and lipids, which can reduce gA-induced pore formation, leading to the decreased ion permeability. [ABSTRACT FROM AUTHOR]

Imidazolium-based ionic surfactants of different sizes were simulated with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) bilayers. Regardless of the phospholipid type, larger surfactants at higher concentrations more significantly insert into the bilayer and increase the bilayer-surface size, in agreement with experiments and previous simulations. Insertion of surfactants only slightly decreases the bilayer thickness, as also observed in experiments. Although the surfactant insertion and its effect on the bilayer size and thickness are similar in different types of bilayers, the volume fractions of surfactants in the bilayer are higher for DMPC bilayers than for POPC and DOPC bilayers. In particular, ionic surfactants with four hydrocarbons yield their volume fractions of 4.6% and 8.7%, respectively, in POPC and DMPC bilayers, in quantitative agreement with experimental values of ∼5% and ∼10%. Also, the inserted surfactants increase the lateral diffusivity of the bilayer, which depends on the bilayer type. These findings indicate that although the surfactant insertion does not depend on the bilayer type, the effects of surfactants on the volume fraction and bilayer dynamics occur more significantly in the DMPC bilayer because of the smaller area per lipid and shorter saturated tails, which helps explain the experimental observations regarding different volume fractions of surfactants in POPC and DMPC bilayers. [ABSTRACT FROM AUTHOR]

We performed coarse-grained molecular dynamics simulations of tachyplesin I (TP-I), which is a β-hairpin antimicrobial peptide with two disulfide bonds, and its linearly extended derivative without disulfide bonds (TPA4) in lipid bilayers for 5 μs. β-hairpin TP-I peptides tend to individually bind to the bilayer surface, while linear TPA4 peptides aggregate and form the β-strand complex on the bilayer surface, indicating the effect of the peptide structure on aggregation. Also, TPA4 more slowly diffuse along the bilayer surface than do TP-I, indicating that aggregated β-strands of TPA4 cannot diffuse as fast as individual β-hairpins of TP-I. TPA4 have the stronger charge interaction with lipid head groups than do TP-I, leading to the deeper insertion into the bilayer. These simulation results indicate that TP-I peptides tend to individually exist on the bilayer surface and thus easily diffuse along the bilayer surface, while TPA4 peptides aggregate as β-strands, which limits the lateral mobility of TPA4, leading to a strong immobilization of TPA4. These findings agree well with the experimentally observed dependence of peptide mobility on the peptide structure in membranes, as well as support experimental suggestions regarding the formation of β-strand complexes of linear TPA4 and the relationship between the peptide aggregation and mobility. [ABSTRACT FROM AUTHOR]

Mixtures of Magainin 2 and PGLa are simulated with 94 nm-sized bilayers composed of phospholipids and lyso-phospholipids for 3 μs using coarse-grained force fields. Calculation of the bilayer bending modulus shows that bilayers become more flexible in the presence of lyso-lipids or peptides, in agreement with experiments. Starting with the initial configuration of peptides randomly distributed on the bilayer surface, peptides aggregate, insert to the bilayer, and form pores. Aggregated peptides do not retain side-by-side heterodimeric structure but instead show the anchoring between C-terminal groups of magainin 2 and PGLa, which allows the deeper insertion of PGLa into the bilayer. In particular, due to the anchoring of magainin 2 and PGLa, the deeply inserted PGLa pull magainin 2 into contact with the edge of the opposite leaflet of the bilayer, which stabilizes the pore. In addition to these biophysical insights, anionic unsaturated-phospholipid bilayers are also simulated to mimic bacterial cell membranes, showing less extent of PGLa insertion and no pore formation. These simulation findings indicate that these synergistic heterodimers have the anchoring structure rather than the side-by-side structure, which supports the experimental observations suggesting the deeper insertion of PGLa and pore formation via the anchoring between anionic C-terminus of magainin 2 and cationic C-terminus of PGLa. Unlabelled Image • The presence of lyso-lipids or peptides decreases bilayer bending moduli • Starting with peptides randomly distributed on bilayer, heterodimers and pores form • Mag-PGLa heterodimers have anchoring structure instead of side-by-side structure • Inserted PGLa pull magainin 2 into the edge of the opposite leaflet of the bilayer • These findings support experiments suggesting heterodimer and pore conformations [ABSTRACT FROM AUTHOR]

The effects of various organic solvents having different H-donor index, asphaltene solubility, and alkyl-substitution on the upgrading of vacuum residue (VR) were investigated under thermal cracking or catalytic hydrocracking conditions at 673 K and 10.0 MPa N 2 or H 2 . Molecular dynamics simulations were also adopted to verify physical interaction between asphaltene species with H-donor solvents. Thermal cracking led to a considerable amount of coke formation, close to 29.8 wt.%, but the addition of H-donors reduced the coke formation down to 23.4, 19.0, 12.4, and 4.1 wt.% in the presence of naphthalene, 1-methyl naphthalene(1-MN), decalin, and tetralin, respectively. The coke formation was considerably reduced to 7.2 wt.% in the hydrocracking condition, and further down to 2.9 and 1.2 wt.% in the presence of naphthalene and tetralin, respectively. It was demonstrated that H-donors retaining the H transfer capability coupled with the solubility of asphaltene contributed to the marked performance of VR hydrocracking in the presence of dispersed MoS 2 catalyst. [ABSTRACT FROM AUTHOR]

Nanopores have been emerged as a powerful tool for analyzing the structural information and interactional properties of a range of biomolecules. The spatial resolution of nanopore is determined by the diameter and effective thickness of its constriction region, but the presence of vestibule or stem structure in protein-based nanopore could negatively affect the sensitivity of the nanopore when applied for genome sequencing and topological analysis of DNA. Recently, alpha-hederin (Ah) has been reported to form a sub-nanometer scale pore structure in lipid membrane. With the simple structure and extremely small effective thickness, the Ah nanopore was shown to discriminate four different types of nucleotides. However, identification of a certain nucleotide in a strand of DNA, which is essential for genome sequencing, remains challenging. Here, we investigated the resolving capability of Ah nanopore to discriminate few nucleotides in a strand of single-stranded DNA, and the factors determining the sensitivity of Ah nanopore. The Ah nanopore was shown to be able to identify as few as three adenosine nucleotides in a strand of poly cytidine, in which the dwell time of the additional current blockade that represents the adenosine residue was in good agreement with their physical length. We also found that the lateral tension and chain pressure generated around the nanopore were influenced by pore's diameter and played as a dependent variables to determine the geometry of nanopore's constriction as well as the spatial resolution of the Ah nanopore. Alpha hederin (Ah) nanopore was synthesized to discriminate the subtle structural difference of nucleotides in a strand of DNA, which is critical for nanopore-based topological analysis of DNA. The Ah nanopore was shown to have a resolving power of identifying as few as three adenosine nucleotides in a strand of poly cytidine. The geometry of pore's constriction region as well as the effective thickness of nanopore, which determine the spatial resolution of nanopore, were found to be regulated by the diameter of Ah nanopore. Image 1 • Identification of nucleotides in stranded form is of importance for genome sequencing. • Ah nanopore with small effective thickness was fabricated by molecular self-assembly. • Diameter-dependent lateral tension determines the spatial resolution of Ah nanopore. • Subtle structural difference between purine and pyrimidine could be discriminated. • Ah nanopore could identify the presence of three adenosines in a strand of poly-C. [ABSTRACT FROM AUTHOR]