Polyhydroxybutyrate (PHB) is a sustainable and compostable polyester, which has great potential for use as food packaging film, having similar barrier properties to conventional plastics. PHB is semi-crystalline and is often copolymerised with polyhydroxyvalerate (PHV) to form poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). Molecular dynamics (MD) simulations provide valuable insight into the polymer structure and gas diffusion, but the accuracy of MD simulations depends on the force field. This work presents a modified all-atom General Amber Force Field that enables PHB, PHV and PHVB copolymers to be modelled. The structural properties of crystal and amorphous phases of PHB and PHV were in good agreement with experiment. The diffusion coefficients of water and oxygen in amorphous PHB were also in good agreement with experimental values. The diffusion coefficient of oxygen in PHV was larger than in PHB, mainly due to the lower density of PHV. The diffusion coefficient of water in PHV was similar to PHB as its diffusion is hindered by the interaction of water with the polar ester groups on the polymer chains. This force field can be used to investigate the diffusion of water and oxygen in PHB, PHV and PHBV copolymers, and to optimise the barrier properties of PHBV-based plastic film.

The receptor binding domain (RBD) of the SARS-CoV-2 spike protein is an important diagnostic and therapeutic target since it binds to the peptidase domain of the angiotensin-converting enzyme 2 (ACE2) receptor, thus facilitating infection by the virus. Many diagnostics utilize the adsorption of proteins onto material surfaces and nanoparticles to create functional couples. In this work, the adsorption of the histidine tag (His-Tag) modified RBD on various inorganic surface models is explored by using fully atomistic molecular dynamics simulations. The material surfaces used are an experimentally relevant negatively charged silica surface, a model positively charged surface, and a self-assembled monolayer terminated with negatively charged carboxyl groups. The simulations with both negatively charged surface models show the protein adsorbing rapidly and specifically, while the protein does not adsorb on the positively charged surface model. Adsorption of the His-Tag modified RBD on both negative surfaces is also favorable for device manufacture, with the protein retaining its structure while its ACE2-binding residues remain free to interact with the environment due to its orientation in the adsorbed state. Consequently, these results can guide the development of new diagnostics through the choice of substrate and protein modification.

Plasticisers are often added to crystallising polymers to improve their processability. Despite many experimental studies, very few modelling studies have been performed to provide fundamental understanding of the impact of plasticisers on polymer cyrstallisation kinetics and thermodynamics. In this work, molecular dynamics simulations are used to study crystallisation in a model linear polymer with plasticiser. We first demonstrate that the plasticiser lowers the amorphous phase glass transition, with the extent of the effect increasing with plasticiser concentration, due to increased polymer mobility. Using a model filler surface to induce crystallisation, we find that the plasticiser also reduces crystallisation and melting temperatures. Furthermore, we find that the plasticiser is expelled from the crystals during growth so that its concentration in the amorphous matrix increases with degree of crystallisation. This has a pronounced consequence for crystal melting, and we find a broad temperature range where the crystal is in equilibrium with the amorphous phase, which we rationalise in terms of free energy changes. This has potentially important consequences for the processing of linear polymers such as polyhydroxybutyrate (PHB), poly(l-lactic acid) (PLLA) and polyvinyl alcohol (PVA), by providing the opportunity for processing the polymer in a semicrystalline rather than fully amorphous state.

Chitosan is a nontoxic biopolymer with many potential biomedical and material applications due to its biodegradability, biocompatibility, and antimicrobial properties. Here, fully atomistic molecular dynamics simulations and enhanced sampling methods have been used to study the adsorption mechanism of chitosan oligomers on a silica surface from an aqueous solution. The free energy of adsorption of chitosan on a silica surface was calculated to be 0.6 kcal mol-1 per monomer in 0.15 mol L-1 aqueous solution, which is comparable to k B T at room temperature. The loading capacity of chitosan on the silica surface was found to be 0.094 mg m-2, and it is dominated by charge compensation. Furthermore, the hydrogen bonding between chitosan and silica was analyzed. The nitrogen and hydroxyl group oxygen chitosan atoms were found to be the main contributors to the hydrogen bonding between chitosan and silica. These findings have the potential to guide the experimental design of chitosan-coated silica nanoparticles for applications such as drug delivery or additives for biopolymer food packaging.

The dynamics of the COVID-19 pandemic is greatly influenced by vaccine quality, as well as by vaccination rates and the behaviour of infected individuals, both of which reflect public health policies. We develop a model for the dynamics of relevant cohorts within a fixed population, taking extreme care to model the reduced social contact of infected individuals in a rigorous self-consistent manner. The basic reproduction number R 0 is then derived in terms of the parameters of the model. Analysis of R 0 reveals two interesting possibilities, both of which are plausible based on known characteristics of COVID-19. Firstly, if the population in general moderates social contact, while infected individuals who display clinical symptoms tend not to isolate, then increased vaccination can drive the epidemic towards a disease-free equilibrium (DFE). However, if the reverse is true, then increased vaccination can destabilise the DFE and yield an endemic state. This surprising result is due to the fact that the vaccines are leaky, and can lead to an increase in asymptomatic individuals who unknowingly spread the disease. Therefore, this work shows that public policy regarding the monitoring and release of health data should be combined judiciously with modeling-informed vaccination policy to control COVID-19.

The structures of the Fc base of various IgG antibodies have been examined with a view to understanding how this region can be used to conjugate IgG to nanoparticles. The base structure is found to be largely consistent across a range of species and subtypes, comprising a hydrophobic region surrounded by hydrophilic residues, some of which are charged at physiological conditions. In addition, atomistic Molecular Dynamics simulations were performed to explore how model nanoparticles interact with the base using neutral and negatively charged gold nanoparticles. Both types of nanoparticle interacted readily with the base, leading to an adaptation of the antibody base surface to enhance the interactions. Furthermore, these interactions left the rest of the domain at the base of the Fc region structurally intact. This implies that coupling nanoparticles to the base of an IgG molecule is both feasible and desirable, since it leaves the antibody free to interact with its surroundings so that antigen-binding functionality can be retained. These results will therefore help guide future attempts to develop new nanotechnologies that exploit the unique properties of both antibodies and nanoparticles.

Abstract The full text of this preprint has been withdrawn by the authors since they no longer stand by the findings/conclusions of this work. Therefore, the authors do not wish this work to be cited as a reference. Questions should be directed to the corresponding author.

Agglomeration is an issue that causes many problems during secondary processing for pharmaceutical companies, causing material to need further processing and costing additional time and resources to ensure a satisfactory outcome. A potential source of agglomeration arises from the particle contacts established during filtration that lead to robust agglomerates forming during drying, so that a necessary first step toward understanding agglomeration is to study the packing properties of filtration beds. Here, we present two and three-dimensional models simulating the formation of packed bed structures during filtration. The models use circular and spherical particles of different sizes, mimicking the bimodal particle size distributions sometimes encountered in industrial practice. The statistics of packing and void formation, along with the distribution of interparticle contacts and percolation structures, are presented and discussed in the context of filtration, drying, and agglomeration. The model paves the way for predictive capabilities that can lead to the rational design of processes to minimize the impact of agglomeration.

Molecular simulations such as Monte Carlo, molecular dynamics, and metadynamics have been used to provide insight into crystallization phenomena, including nucleation and crystal growth. However, these simulations depend on the force field used, which models the atomic and molecular interactions, to adequately reproduce relevant material properties for the phases involved. Two widely used force fields, the General AMBER Force Field (GAFF) and the Optimized Potential for Liquid Simulations (OPLS), including several variants, have previously been used for studying urea crystallization. In this work, we investigated how well four different versions of the GAFF force field and five different versions of the OPLS force field reproduced known urea crystal and aqueous solution properties. Two force fields were found to have the best overall performance: a specific urea charge-optimized GAFF force field and the original all-atom OPLS force field. It is recommended that a suitable testing protocol involving both solution and solid properties, such as that used in this work, is adopted for the validation of force fields used for simulations of crystallization phenomena.

Abstract The signalling mechanism of G-protein coupled receptors has been broadly studied, however, due to their structural complexity, details of the signalling pathway remain unclear. Here we present molecular dynamics (MD) simulations that reveal the conformational changes of the GnRH receptor (GnRH1R) induced by interaction with the gonadotropin-releasing hormone (GnRH). A comparison between the GnRH1R conformation in the absence and presence of GnRH reveals specific conformational differences that characterise an active and inactive state of the receptor. Furthermore, we describe a detailed cascade of ligand-induced conformational changes in the GnRH receptor that can lead to intracellular signal transmission. We observe that following the initial interaction of GnRH, the signal travels via a particular activation switch triad (Glu90-Lys121-Ser124). This acts as the driving force for an intracellular loop to reposition and expose the G-protein orthosteric pocket. In contrast, in the absence of GnRH, the receptor adopts an inactive conformation, where the activation switch residues are separated while the G-protein binding site is sterically blocked. These findings will aid the discovery of new pharmaceuticals targeting GnRH1R, and they broaden understanding of the signal transmission process and hence the functionality of G-protein coupled receptors in general.

Recently, much research is focused on the use of photothermal therapy (PTT) as an advanced method to treat various types of cancer. The PTT approach primarily utilizes nanoparticles (NPs) made from metals, carbon, or semiconductors that can convert near-infrared laser irradiation, which penetrates tissues, into local heat that induces cancer cell death. An alternative approach is to utilize NPs (such as liposomes) to carry suitable dye molecules to the same end. Numerous studies concerning PTT have shown that local heat released in cancer cells may suppress the expression of membrane transporter proteins such as P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1), thus enhancing cytotoxicity and reverse multidrug resistance. In addition, because NPs may be loaded with different substances, researchers have designed multifunctional NPs for PTT by including several agents such as membrane transporter modulators, anticancer drugs, and photothermal agents. This review will focus on the recent advances in PTT utilizing various types of NPs, and their components and characteristics. In addition, the role of membrane transporters in PTT will be highlighted and different methods of transporter modulation will be summarized from several PTT studies in which multifunctional NPs were used to treat cancers in vitro and in vivo.

Understanding the binding of chitosan oligomers to the surface of a chitin nanocrystal is important for improving the enzymatic deacetylation of chitin and for the design of chitin/chitosan composite films. Here, we study the binding of several chito-oligomers to the (100) surface of an alpha-chitin crystal using molecular dynamics (MD), steered MD, and umbrella sampling. The convergence of the free energy was carefully considered and yielded a binding energies of -12.5 and -2 kcal mol(-1) for 6-monomer-long chitin and uncharged chitosan oligomers, respectively. We also found that the results for the umbrella sampling were consistent with the force profile from the steered MD and with classical MD simulations of the adsorption process. Our results give insight into the molecularscale interactions, which can be helpful for the design of new chitin composite films. Furthermore, the free energy curves we present can be used to validate coarse-grained models for chitin and chitosan, which are necessary to study the selfassembly of chitin crystals due to the long time scale of the process.

Filler particles are known to act as nucleants for polymer crystallisation yet the connection between the filler surface properties and polymer crystallisation are not well understood. In this work, molecular dynamics simulations were used to investigate homogeneous and heterogeneous polymer nucleation and crystallisation using a generic linear bead–spring polymer model with a bond bending potential. The polymer systems were equilibrated at high temperature and then cooled at a constant rate. Without a surface present, polymers with stiff chains were found to crystallise more readily than more flexible polymers. The degree of crystallinity was estimated based on the mass fraction of straight chain segments which we equate to stem mass fraction. At a temperature Tc a sharp increase in density, radius of gyration and stem mass fraction occurred. After cooling, the systems were reheated and some systems showed hysteresis with a sharp decrease in these properties occurring upon melting at Tm>Tc. For slower heating rates, crystal growth occurred during heating from between the glass transition temperature, Tg, and Tc until just before melting at Tm. The presence of an isotropic surface was found to promote crystallisation in flexible systems that did not crystallise in the bulk, where the stem mass fraction and Tc increased with the interaction strength between the surface and the polymer beads. Changes in Tc and degree of crystallinity with cooling rate are consistent with experimental observations. This model captures polymer crystallisation phenomena and provides insight into heterogeneous nucleation, demonstrating that strong interfacial interactions promote crystallisation, thus aiding the choice or design of nucleants for control of polymer crystallisation and microstructure.

Polyhydroxybutyrate (PHB) is a sustainable polymer that is a promising candidate for replacing petroleum-based plastics in food packaging. Fillers are used to improve the mechanical properties of PHB composites, simultaneously changing the crystallinity of the polymer matrix. However, it is not well understood how fillers affect crystallisation and microstructure, and thus the resulting mechanical properties of the composite. This review summarises simulation work on polymer nucleation and crystallisation and how nucleation is influenced by different types of polymer-filler interfaces. Experimental studies of PHB composites with a wide variety of fillers are reviewed to find trends between the filler type, crystallinity and mechanical properties. It is clear that fillers act as nucleants that increase the number of spherulites while reducing spherulite size. This behaviour is apparent for almost all fillers regardless of filler chemistry or topology. However, the data obtained from the literature do not seem to produce strong conclusions about the effect of the degree of crystallinity on the tensile properties of PHB-filler composites, although there are some weak trends that indicate the importance of microstructure. In order to enable prediction and control of PHB composite properties, further systematic studies are required to elucidate the effect of specific filler types and the connection between crystallinity, microstructure and mechanical properties. (c) 2022 The Authors. Polymer International published by John Wiley & Sons Ltd on behalf of Society of Industrial Chemistry.

Staphylococcus protein A (SpA) is found in the cell wall of Staphylococcus aureus bacteria. Its ability to bind to the constant Fc regions of antibodies means it is useful for antibody extraction, and further integration with inorganic materials can lead to the development of diagnostics and therapeutics. We have investigated the adsorption of SpA on inorganic surface models such as experimentally relevant negatively charged silica, as well as positively charged and neutral surfaces, by use of fully atomistic molecular dynamics simulations. We have found that SpA, which is itself negatively charged at pH7, is able to adsorb on all our surface models. However, adsorption on charged surfaces is more specific in terms of protein orientation compared to a neutral Au (111) surface, while the protein structure is generally well maintained in all cases. The results indicate that SpA adsorption is optimal on the siloxide-rich silica surface, which is negative at pH7 since this keeps the Fc binding regions free to interact with other species in solution. Due to the dominant role of electrostatics, the results are transferable to other inorganic materials and pave the way for new diagnostic and therapeutic designs where SpA might be used to conjugate antibodies to nanoparticles.

Classical molecular dynamics simulations were used to investigate how dispersion (van der Waals) interactions between non-polar, hydrophobic surfaces and aqueous glycine solutions affect the solution composition, molecular orientation, and dynamics at the interface. Simulations revealed that dispersion interactions lead to a major increase in the concentration of glycine at the interface in comparison with the bulk solution, resulting from a competition between solute and solvent molecules to be or not to be near the interface. This can then lead to kinetic and/or structural effects facilitating heterogeneous nucleation of glycine at non-polar surfaces, in agreement with recent observations for tridecane, graphene, and polytetrafluoroethylene. A novel parameterization process was developed to map a model surface with tunable dispersion interactions to heptane, tridecane, and graphite materials. The model surface was capable of reproducing the solution structure observed in fully atomistic simulations with excellent agreement and also provided good agreement for dynamic properties, at a significantly reduced computational cost. This approach can be used as an effective tool for screening materials for heterogeneous nucleation enhancement or suppression, based on non-specific dispersion interactions based on bulk material molecular properties, rather than interfacial functional groups, templating or confinement effects.

Antibodies play a crucial role in the immune response, in fighting off pathogens as well as helping create strong immunological memory. Antibody-dependent enhancement (ADE) occurs when non-neutralising antibodies recognise and bind to a pathogen, but are unable to prevent infection, and is widely known and is reported as occurring in infection caused by several viruses. This narrative review explores the ADE phenomenon, its occurrence in viral infections and evaluates its role in infection by SARS-CoV-2 virus, which causes coronavirus disease 2019 (COVID-19). As of yet, there is no clear evidence of ADE in SARS-CoV-2, though this area is still subject to further study.

We study crystalline surface evolution in extreme environments, where high-energy atoms impinge on a crystalline surface to cause sputtering, growth and surface roughening. For our model system, we study the evolution of the Ni(111) surface under Ni atom bombardment, using Molecular Dynamics (MD) simulation and a Sutton-Chen force field, where the uppermost surface layers are free to move, supported by thermostatically controlled layers above a rigid template. The MD statistics of sputtering and sticking are used to aid the development of a computationally efficient kinetic Monte Carlo (KMC) code. Comparisons between the simulation surface morphologies are used to tune the KMC growth rules so that the key statistical features of the MD structures are captured by the KMC model. This model is then employed to explore the predicted behaviour over length and times scales much larger than those accessible to MD. While the MD-KMC approach is well known, this application to the complex surface growth encountered in energetic atomic bombardment illuminates the complexities of relating atomistic events to morphological evolution. The work shows how simulation methodology can be extended to provide predictive capabilities, paving the way for design tools for engineering processes such as plasma deposition film growth.

Nanoparticles are small particles sized 1-100 nm, which have a large surface-to-volume ratio, allowing efficient adsorption of drugs, proteins, and other chemical compounds. Consequently, functionalized nanoparticles have potential diagnostic and therapeutic applications. A variety of nanoparticles have been studied, including those constructed from inorganic materials, biopolymers, and lipids. In this review, we focus on recent work targeting the severe acute respiratory syndrome coronavirus 2 virus that causes coronavirus disease (COVID19). Understanding the interactions between coronavirusspecific proteins (such as the spike protein and its host cell receptor angiotensin-converting enzyme 2) with different nanoparticles paves the way to the development of new therapeutics and diagnostics that are urgently needed for the fight against COVID-19, and indeed for related future viral threats that may emerge.