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Hypothesis Delivery of multiple payloads using the same micelle is of significance to achieve multifunctional or synergistic effects. The interacting distribution of different payloads in micelles is expected to influence the loading stability and capacity. It is highly desirable to explore how intermolecular interactions affect the joint distribution of multi-payloads. Experiments Dissipative Particle Dynamics simulations were performed to probe the loading of three payloads: decane with a linear carbon chain, butylbenzene with an aromatic ring connected to carbon chain, and naphthalene with double aromatic rings, within poly(β-amino ester)-b-poly(ethylene glycol) micelles. Properties of core-shell micelles, e.g., morphological evolution, radial density distribution, mean square displacement, and contact statistics, were analyzed to reveal payloads loading stability and capacity. Explorations were extended to vesicular, multi-compartment, double helix, and layer-by-layer micelles with more complex inner structures. Findings Different payloads have their own preferred locations. Decane locates at the hydrophilic/hydrophobic interface, butylbenzene occupies both the hydrophilic/hydrophobic interface and the hydrophobic core, while naphthalene enters the hydrophobic core. More efficient delivery of multi-payloads is achieved since the competition of payloads occupying preferred locations is minimized. The fusion of micelles encapsulating different payloads suggests that specific payloads will move to their preferred positions without interfering other payloads.

An unprecedented fully reduced {MoV60} POM served as a cheap and robust molecular light-absorber model possessing wide light absorption and was applied to build a co-sensitized solar cell photoelectronic device.

SARS-CoV-2 Spike is a key protein that mediates viral entry into cells and elicits antibody responses. Its importance in infection, diagnostics, and vaccinations has created a large demand for purified Spike for clinical and research applications. Spike is difficult to express, prompting modifications to the protein and expression platforms to improve yields. Alternatively, the Spike receptor-binding domain (RBD) is commonly expressed with higher titers, though it has lower sensitivity in serological assays. Here, we improve transient Spike expression in Chinese hamster ovary (CHO) cells. We demonstrate that Spike titers increase significantly over the expression period, maximizing at 14mgL-1 on day 7. In comparison, RBD titers peak at 54mgL-1 on day 3. Next, we develop eight Spike truncations (T1-T8) in pursuit of truncation with high expression and antibody binding. The truncations T1 and T4 express at 130 and 73mgL-1 , respectively, which are higher than our RBD titers. Purified proteins were evaluated for binding to antibodies raised against full-length Spike. T1 has similar sensitivity as Spike against a monoclonal antibody and even outperforms Spike for a polyclonal antibody. These results suggest that T1 is a promising Spike alternative for use in various applications.

The binding interaction between the T-cell receptor (TCR) and peptide-major histocompatibility complex (pMHC) is modulated by several factors (known and unknown), however, investigations into effects of glycosylation are limited. A fully glycosylated computational model of the TCR bound to the pMHC is developed to investigate the effects of glycosylation on dissociation kinetics from the pMHC. Here, we examine the effects of N-glycosylation on TCR-pMHC bond strength using steered molecular dynamic simulations. N-glycosylation is a post-translational modification that adds sugar moieties to molecules and can modulate the activity of several immune molecules. Using a TCR-pMHC pair found in melanoma as a case study, our study demonstrates that N-glycosylation of the TCR-pMHC alters the proteins’ conformation; increases the bond lifetime; and increases the number of hydrogen bonds and Lennard-Jones Contacts involved in the TCR-pMHC bond. We find that weak glycan-protein or glycan-glycan interactions impact the equilibrated structure of the TCR and pMHC leading to an increase in the overall bond strength of the TCR-pMHC complex including the duration and energetic strength under constant load. These results indicate that N-glycosylation plays an important role in the TCR-pMHC bond and should be considered in future computational and experimental studies. Communicated by Ramaswamy H. Sarma

T Cell Receptor (TCR) recognition of a peptide-major histocompatibility complex (pMHC) is a crucial component of the adaptive immune response. The identification of therapeutically relevant TCR-pMHC pairs is a significant bottleneck in the implementation of TCR-based immunotherapies but may be augmented by computational methodologies. The ability to computationally design TCRs to target a specific pMHC will require an automated integration of next-generation sequencing, protein-protein structure prediction, molecular dynamics (MD), and TCR ranking. We present a generic pipeline to evaluate patient-specific, sequence-based TCRs to a target pMHC. Using the three most frequently expressed TCRs from 16 colorectal cancer patients, we predicted the protein-protein structure of the TCRs to the target CEA peptide-MHC using Modeller and ColabFold. Then, these TCR-pMHC structures were compared by performing an automated molecular dynamics equilibration. ColabFold generates starting configurations that require, on average, a ~2.5X reduction in simulation time to equilibrate TCR-pMHC structures compared to Modeller. In addition, the structural differences between Modeller and ColabFold are demonstrated by an increase in root mean square deviation (~0.20 nm) between clusters of equilibrated configurations, which can impact the number of hydrogen bonds and Lennard-Jones contacts between the TCR and pMHC. Finally, we identify a TCR ranking criteria that may be used to prioritize TCRs for evaluation of in vitro immunogenicity.

To design drug-delivery agents for therapeutic and diagnostic applications, understanding the mechanisms by which covalently functionalized carbon nanotubes penetrate and interact with cell membranes is of great importance. Here, we report all-atom molecular dynamics results from polystyrene and carboxyl-terminated polystyrene-modified carbon nanotubes and show their translocation behavior across a model lipid bilayer together with their potential to deliver a molecule of the drug ibuprofen into the cell. Our results indicate that functionalized carbon nanotubes are internalized by the membrane in hundreds of nanoseconds and that drug loading increases the internalization speed further. Both loaded and unloaded tubes cross the closest leaflet of the bilayer by nonendocytic pathways, and for the times studied, the drug molecule remains trapped inside the pristine tube while remaining attached at the end of polystyrene-modified tube. On the other hand, carboxyl-terminated polystyrene functionalization allows the drug to be completely released into the lower leaflet of the bilayer without imposing damage to the membrane. This study shows that polystyrene functionalization is a promising alternative and facilitates drug delivery as a benchmark case.

Understanding emergent phenomena of fluids under physical confinement requires the development of advanced tools for rapid and accurate simulation of their physiochemical properties. Simulating liquid molecules commensurate in size with the nanoscale enclosures that confine them is a key challenge. We demonstrate an accelerated molecular dynamics simulation technique that combines soft-core potentials (SCP) and simulated annealing (SA) to analyze confined liquids. This integrated SCP/SA method relies on a new spliced soft-core potential (SSCP), which enables tunable accuracy with respect to the target hard-core potential (HCP). SCP/SA enables the packing of enclosures with bulk material in a controlled, thermodynamically consistent manner. The enhanced SSCP accuracy is a critical feature of SCP/SA, enabling a smooth transition between the SCP and the HCP at a desired SCP hardness. We applied SCP/SA to the problem of filling a carbon nanotube (CNT) in periodic boundary conditions with a popular ionic liquid (IL), 1-butyl-3-methylimidazolium hexafluorophosphate [BMIM

We present a general approach to isolate chemical reaction mechanism as an independently controllable variable across chemically distinct systems. Modern approaches to reduce the computational expense of molecular dynamics simulations often group multiple atoms into a single "coarse-grained" interaction site, which leads to a loss of chemical resolution. In this work we convert this shortcoming into a feature and use identical coarse-grained models to represent molecules that share non-reactive characteristics but react by different mechanisms. As a proof of concept we use this approach to simulate and investigate distinct, yet similar, trifunctional isocyanurate resin formulations that polymerize by either chain- or step-growth. Since the underlying molecular mechanics of these models are identical, all emergent differences are a function of the reaction mechanism only. We find that the microscopic morphologies resemble related all-atom simulations and that simulated mechanical testing reasonably agrees with experiment.

SARS-CoV-2 Spike is a key protein that mediates viral entry into cells and elicits antibody responses. Its importance in infection, diagnostics, and vaccinations has created a large demand for purified Spike for clinical and research applications. Spike is difficult to express, prompting modifications to the protein and expression platforms to improve yields. Alternatively, Spike receptor binding domain (RBD) is commonly expressed with higher titers, though it has lower sensitivity in serological assays. Here, we improve transient Spike expression in Chinese hamster ovary (CHO) cells. We demonstrate that Spike titers increase significantly over the expression period, maximizing at 14 mg/L at day 7. In comparison, RBD titers peak at 54 mg/L at day 3. Next, we develop 8 Spike truncations (T1-T8) in pursuit of a truncation with high expression and antibody binding. The truncations T1 and T4 express at 130 mg/L and 73 mg/L, respectively, which are higher than our RBD titers. Purified proteins were evaluated for binding to antibodies raised against full-length Spike. T1 has similar sensitivity as Spike against a monoclonal antibody and even outperforms Spike for a polyclonal antibody. These results suggest T1 is a promising Spike alternative for use in various applications.

Fully reduced polyoxometalates are predicted to give rise to a broad and strong absorption spectrum, suitable energy levels, and unparalleled electronic and optical properties. However, they are not available to date. Here, an unprecedented fully reduced polyoxomolybdate cluster, namely Na

Atomic vibrations can inform about materials properties from hole transport in organic semiconductors to correlated disorder in metal-organic frameworks. Currently, there are several methods for predicting these vibrations using simulations, but the accuracy-efficiency tradeoffs have not been examined in depth. In this study, rubrene is used as a model system to predict atomic vibrational properties using six different simulation methods: density functional theory, density functional tight binding, density functional tight binding with a Chebyshev polynomial-based correction, a trained machine learning model, a pretrained machine learning model called ANI-1, and a classical forcefield model. The accuracy of each method is evaluated by comparison to the experimental inelastic neutron scattering spectrum. All methods discussed here show some accuracy across a wide energy region, though the Chebyshev-corrected tight-binding method showed the optimal combination of high accuracy with low expense. We then offer broad simulation guidelines to yield efficient, accurate results for inelastic neutron scattering spectrum prediction.

An atomic-scale mechanism describing the role of mechanosensing in T Cell Receptor (TCR) recognition of peptides in the binding groove of the peptide-major histocompatibility complex (pMHC) may inform the design of novel TCRs for immunotherapies. Using steered molecular dynamic simulations, our study demonstrates that mutations to peptides in the binding groove of the pMHC – which are known to discretely alter the T cell response to an antigen – influence MHC conformation and thus the overall strength of the TCR-pMHC bond including duration and length under constant load. Moreover, physiochemical features of the TCR-pMHC dynamic bond strength, such as hydrogen bonds and Lennard-Jones contacts, correlate with the immunogenic response elicited by the specific peptide in the MHC groove. Thus, formation of transient TCR-pMHC bonds is a characteristic of immunogenic peptides and is mediated by stabilized interactions.x

Plant biotechnology journal 19(10), 1921-1936 (2021). doi:10.1111/pbi.13658, Published by Wiley-Blackwell, Oxford

The recently discovered, membrane-active peptide LBF14 contains several non-proteinogenic amino acids and is able to transform vesicles into tubule networks. The exact membrane interaction mechanism and detailed secondary structure are yet to be determined. We performed molecular dynamics simulations of LBF14 and let it fold de novo into its ensemble of native secondary structures. Histidine protonation state effects on secondary structure were investigated. An MD simulation of the peptide with a lipid bilayer was performed. Simulation results were compared to circular dichroism and electron paramagnetic resonance data of previous studies. LBF14 contains a conserved helical section in an otherwise random structure. Helical stability is influenced by histidine protonation. The peptide localized to the polar layer of the membrane, consistent with experimental results. While the overall secondary structure is unaffected by membrane interaction, Ramachandran plot analysis yielded two distinct peptide conformations during membrane interaction. This conformational change was accompanied by residue repositioning within the membrane. LBF14 only affected the local order in the membrane, and had no measurable effect on pressure. The simulation results are consistent with the previously proposed membrane interaction mechanism of LBF14 and can additionally explain the local interaction mechanism. Communicated by Ramaswamy H. Sarma.

Highly detailed steered Molecular Dynamics simulations are performed on differently glycosylated receptor binding domains of the SARS-CoV-2 spike protein. The binding strength and the binding range increases with glycosylation. The interaction energy rises very quickly with pulling the proteins apart and only slowly drops at larger distances. We see a catch slip type behavior where interactions during pulling break and are taken over by new interactions forming. The dominant interaction mode are hydrogen bonds but Lennard-Jones and electrostatic interactions are relevant as well.Statement of SignificanceGlycosylation of the receptor binding domain of the Spike protein of SARS-CoV-2 as well as the ACE2 receptor leads to stronger and longer ranged binding interactions between the proteins. Particularly, at shorter distances the interactions are between residues of the proteins themselves whereas at larger distances these interactions are mediated by the glycans.Abstract Figure

The use of coordination complexes as building units within covalent organic frameworks (COFs) has significant potential to diversify the structures and properties of this class of materials. Here, we present a synergistic coordination and reticular chemistry approach to the design of a series of crystalline scandium–covalent organic frameworks (Sc–COFs), featuring tunable levels of metal incorporation. Removal of scandium from the material with the highest metal content results in a metal-imprinted COF (MICOF) that exhibits high affinity and capacity for Sc3+ ions in acidic environments and in the presence of competing metal ions. In particular, the selectivity of this MICOF for Sc3+ over common impurity ions such as La3+ and Fe3+ surpasses that of all reported scandium adsorbents. Importantly, analogous materials can be prepared starting from earth-abundant transition metals, highlighting the versatility of this approach for the development of tailor-made metal–COFs and MICOFs for applications involving selective metal ion capture.

Inelastic neutron scattering (INS) provides a weighted density of phonon modes. Currently, INS spectra can only be interpreted for perfectly crystalline materials because of high computational cost for electronic simulations. INS has the potential to provide detailed morphological information if sufficiently large volumes and appropriate structural variety are simulated. Here, we propose a method that allows direct comparison between INS data with molecular dynamics simulations, a simulation method that is frequently used to simulate semicrystalline/amorphous materials. We illustrate the technique by analyzing spectra of a well-studied conjugated polymer, poly(3-hexylthiophene-2,5-diyl) (P3HT) and conclude that our technique provides improved volume and structural variety, but that the classical force field requires improvement before the morphology can be accurately interpreted.

Lewis pairs (LPs) with outstanding performance for nonmetal‐mediated catalysis reactions have high fundamental interest and remarkable application prospects. However, their solubility characteristics lead to instability and deactivation upon recycling. Here, the layered porous aromatic framework (PAF‐6), featuring two kinds of Lewis base sites (NPiperazine and NTriazine), is exfoliated into few‐layer nanosheets to form the LP entity with the Lewis acid. After comparison with various porous networks and verification by density functional theory (DFT) calculations, the NTriazine atom in the specific spatial environment is determined to preferably coordinate with the electron‐deficient boron compound in a sterically hindered pattern. LP‐bare porous product displays high catalytic activity for the hydrogenation of both olefin and imine compounds, and demonstrates ≈100% activity after 10 successful cycles in hydrogenation reactions. Considering the natural advantage of porous organic frameworks to construct LP groups opens up novel prospects for preparing other nonmetallic heterogeneous catalysts for efficient and recyclable catalysis., A porous aromatic framework featuring two kinds of Lewis base sites (NPiperazine and NTriazine) is exfoliated into few‐layer nanosheets to form a Lewis pair (LP) group with the Lewis acid in situ. This LP‐bare porous product with the significant catalysis performance opens up prospects for preparing other nonmetallic heterogeneous catalysts.

We develop fully glycosylated computational models of ACE2-Fc fusion proteins which are promising targets for a COVID-19 therapeutic. These models are tested in their interaction with a fragment of the receptor-binding domain (RBD) of the Spike Protein S of the SARS-CoV-2 virus, via atomistic molecular dynamics simulations. We see that some ACE2 glycans interact with the S fragments, and glycans are influencing the conformation of the ACE2 receptor. Additionally, we optimize algorithms for protein glycosylation modelling in order to expedite future model development. All models and algorithms are openly available.

While self-assembly of molecules is relatively well-known and frequently utilized in chemical synthesis and material science, controlled assembly of molecules represents a new concept and approach. The present work demonstrates the concept of controlled molecular assembly using a non-spherical biomolecule, heparosan tetrasaccharide (MW = 1.099 kD). The key to controlled assembly is the fact that ultra-small solution droplets exhibit different evaporation dynamics from those of larger ones. Using an independently controlled microfluidic probe in an atomic force microscope, sub-femtoliter aqueous droplets containing designed molecules produce well-defined features with dimensions as small as tens of nanometers. The initial shape of the droplet and the concentration of solute within the droplet dictate the final assembly of molecules due to the ultrafast evaporation rate and dynamic spatial confinement of the droplets. The level of control demonstrated in this work brings us closer to programmable synthesis for chemistry and materials science which can be used to develop vehicles for drug delivery three-dimensional nanoprinting in additive manufacturing.

Improving the mechanical performance of nanocrystalline functional oxides can have major implications for stability and resilience of battery cathodes, development of reliable nuclear oxide fuels, strong and durable catalytic supports. By combining Monte Carlo simulations, experimental thermodynamics, and in-situ transmission electron microscopy, we demonstrate a novel toughening mechanism based on interplay between the thermo-chemistry of the grain boundaries and crack propagation. By using zirconia as a model material, lanthanum segregation to the grain boundaries was used to increase the toughness of individual boundaries and simultaneously promote a smoother energy landscape in which cracks experience multiple deflections through the grain boundary network, ultimately improving fracture toughness.

This study uses an all-atom computational model to investigate the temperature dependent heterogeneity and percolation in a nanofilm system of short linear epoxy chains on a solid graphene surface. The heterogeneity, which indicates having physical characters that vary within the nanofilm, is mainly manifested in distributions of volume, energy and the dynamic properties. Local glass transition temperatures, Tgs, from above properties depend largely on the separation to the graphene surface, and the glass transition of the nanofilm is asynchronous along the film normal. Distinct Tg increases and decreases are particularly observed in the solid and free interfaces, respectively, compared with the bulk. From the dynamic heterogeneity, percolation effect, which indicates the connectivity of mobile and immobile domains, of the nanofilm is also observed during glass transition by plotting internal atomic mobility distribution diagrams. A multi-stage percolation mechanism based on the glass transition state and the connection state of immobile and mobile domains of the nanofilm is developed. A relatively immobile domain near the graphene surface is observed, even at temperatures much higher than Tg, and it initiates the dynamic percolation. The interconnection of immobile domains after percolation accelerate the transition from the rubbery to the glassy state.

We present a coarse-grained MARTINI model for methylene blue (MB) and investigate the interactions of MB with dioleylphosphatidylcholine (DOPC) lipid bilayers by molecular dynamics simulations. Our results show that the charge state of MB and the oxidation degree of the DOPC bilayer play critical roles on membrane properties. Oxidation of the DOPC bilayer significantly increases permeability of water and MB molecules, irrespective of the charge state of MB. The most significant changes in membrane properties are obtained for peroxidized lipid bilayers in the presence of cationic MB, with ∼11% increase in the membrane area per lipid head group and ∼7 and 44% reduction in membrane thickness and lateral diffusivity, respectively.

© 2018 the Owner Societies. The effect of La3+doping on the structure and ionic conductivity change in nanocrystalline yttria-stabilized zirconia (YSZ) was studied using a combination of Monte Carlo and molecular dynamics simulations. The simulation revealed the segregation of La3+at eight tilt grain boundary (GB) structures and predicted an average grain boundary (GB) energy decrease of 0.25 J m-2, which is close to the experimental values reported in the literature. Cation stabilization was found to be the main reason for the GB energy decrease, and energy fluctuations near the grain boundary are smoothed out with La3+segregation. Both dynamic and energetic analysis on the Σ13(510)/[001] GB structure revealed La3+doping hinders O2-diffusion in the GB region, where the diffusion coefficient monotonically decreases with increasing La3+doping concentration. The effect was attributed to the increase in the site-dependent migration barriers for O2-hopping caused by segregated La3+, which also leads to anisotropic diffusion at the GB.

An atomic-level molecular dynamics simulation was carried out to study the effects of a plant sterol (sitosterol) and glucosylceramide (GlcCer) on a 1,2-dilinoleoylposphocholine (DLiPC) membrane. Initially, a membrane containing 50mol% sitosterol was compared with that containing the same ratio of cholesterol. These simulations showed differential condensing and ordering effects of sitosterol and cholesterol, with cholesterol being slightly more efficient than sitosterol in packing the membrane more tightly to a liquid ordered phase. By incorporation of 9.3% GlcCer on DLiPC/sterol membrane no notable change was observed in terms of area per lipid, bilayer thickness, order parameter and lateral diffusion. Some clusters of GlcCer/sterol were observed at higher ratio of GlcCer (15.5%), supporting the existence of GlcCer/sitosterol-enriched Lo-domains on the nanometer scale in the plant lipid mixture.

This editorial discusses the broad range and scope of this special issue of Soft Materials. All articles deal with the challenge to model and/or simulate various types of systems of soft matter. De...

The asymmetric hydrogenation of biomass-derived molecules for the preparation of single enantiomer compounds is an effective method to reduce the rapid consumption of fossil resources. Porous organic frameworks (POFs) with pure organic surfaces may provide unusual confinement effects for organic substrates in chiral catalysis. Here, a series of POF catalysts are designed with chiral active centers decorated into sharply defined one-dimensional channels with diameters in the range of 1.2-2.9 nm. Due to the synergistic effect originating from the conjugated inner wall, the POF material (aperture size 2.4 nm) concentrates over 90% of aromatic species into the porous architecture, and its affinity is one or two orders of magnitude higher than those of classical porous solids. As determined by PBE+D3 calculation, the phenyl fragment reveals strong π-π interaction for steric hindrance around the metal active site to achieve stronger asymmetric induction. Therefore, this POF catalyst achieves high conversion (>99% yield) and enantioselectivity (>99% ee) for various substrates. The advantages of using the POF platform as a chiral catalyst can provide new perspectives on POF-based solid-state host-guest chemistry and asymmetric heterogeneous catalysis.