Hierarchical Coarse-Grained Strategy for Macromolecular Self-Assembly: Application to Hepatitis B Virus-Like Particles

Macromolecular self-assembly is at the basis of many phenomena in material and life sciences that find diverse applications in technology. One example is the formation of virus-like particles (VLPs) that act as stable empty capsids used for drug delivery or vaccine fabrication. Similarly to the capsid of a virus, VLPs are protein assemblies, but their structural formation, stability, and properties are not fully understood, especially as a function of the protein modifications. In this work, we present a data-driven modeling approach for capturing macromolecular self-assembly on scales beyond traditional molecular dynamics (MD), while preserving the chemical specificity. Each macromolecule is abstracted as an anisotropic object and high-dimensional models are formulated to describe interactions between molecules and with the solvent. For this, data-driven protein–protein interaction potentials are derived using a Kriging-based strategy, built on high-throughput MD simulations. Semi-automatic supervised learning is employed in a high performance computing environment and the resulting specialized force-fields enable a significant speed-up to the micrometer and millisecond scale, while maintaining high intermolecular detail. The reported generic framework is applied for the first time to capture the formation of hepatitis B VLPs from the smallest building unit, i.e., the dimer of the core protein HBcAg. Assembly pathways and kinetics are analyzed and compared to the available experimental observations. We demonstrate that VLP self-assembly phenomena and dependencies are now possible to be simulated. The method developed can be used for the parameterization of other macromolecules, enabling a molecular understanding of processes impossible to be attained with other theoretical models

DEM simulation of wood pellets dynamics in a mechanically fluidized reactor

The Mechanically Fluidized Reactor (MFR) is a novel technology developed to perform fast pyrolysis of solid biomass with particle size between 4 to 8 mm (1). The MFR has been developed to treat cohesive and thermally sensitive biomass materials. This technology does not require any fluidization gas, therefore the residence time of the vapors is solely controlled by their production rate. In order to get better process understanding and to optimize the process, the particle dynamics in the MFR has been numerically investigated in this contribution. The cylindrical apparatus with a stirrer consisting of vertical blades has been modeled (Fig. 1a). The simulations have been performed in the in-house developed simulation framework MUSEN (2), which is based on the Discrete Element Method (DEM). All particles in the apparatus (foamed glass beads and wood pellets) have been considered individually and for all particles the Newtonian equations of motion have been solved (Fig. 1b). Please click Additional Files below to see the full abstract

Fabrication of composites via spouted bed granulation process and simulation of their micromechanical properties

In this contribution numerical simulation of Young’s modulus of copper-polymer composites is presented. For the simulation of the composites the Bonded-Particle-Model was applied. The model allows representing of the structure of composite materials realistically. The polymer matrix, which surrounds the particles, was represented as network of solid bonds connecting copper particles. Simulation results were validated based on mechanical determination of modulus of elasticity. The modulus of elasticity was approximated in experiments as well as in simulation by four-point-bending tests. It was observed, that obtained simulation results are in good agreement with experimental results

Modelling of Mechanical Behavior of Biopolymer Alginate Aerogels Using the Bonded-Particle Model

A novel mesoscale modelling approach for the investigation of mechanical properties of alginate aerogels is proposed. This method is based on the discrete element method and bonded-particle model. The nanostructure of aerogel is not directly considered, instead the highly porous structure of aerogels is represented on the mesoscale as a set of solid particles connected by solid bonds. To describe the rheological material behavior, a new elastic-plastic functional model for the solids bonds has been developed. This model has been derived based on the self-similarity principle for the material behavior on the macro and mesoscales. To analyze the effectiveness of the proposed method, the behavior of alginate aerogels with different crosslinking degrees (calcium content) was analyzed. The comparison between experimental and numerical results has shown that the proposed approach can be effectively used to predict the mechanical behavior of aerogels on the macroscale

Dyssol — an open-source flowsheet simulation framework for particulate materials

Dyssol is a modelling framework for the dynamic flowsheet simulation of processes designed for handling of particulate materials. Main distinctive features of this software are the comprehensive description of multidimensionally distributed particulate materials, the application of transformation matrices and the use of sequential-modular simulation approach. This cross-platform system can be easily extended with new models, applied for calculation of large datasets and coupled to the external programme packages

Modelling of mechanical behavior of biopolymer alginate aerogels using the bonded-particle model

A novel mesoscale modelling approach for the investigation of mechanical properties of alginate aerogels is proposed. This method is based on the discrete element method and bonded-particle model. The nanostructure of aerogel is not directly considered, instead the highly porous structure of aerogels is represented on the mesoscale as a set of solid particles connected by solid bonds. To describe the rheological material behavior, a new elastic-plastic functional model for the solids bonds has been developed. This model has been derived based on the self-similarity principle for the material behavior on the macro and mesoscales. To analyze the effectiveness of the proposed method, the behavior of alginate aerogels with different crosslinking degrees (calcium content) was analyzed. The comparison between experimental and numerical results has shown that the proposed approach can be effectively used to predict the mechanical behavior of aerogels on the macroscale

Numerical investigation of compaction of deformable particles with bonded-particle model

In this contribution, a novel approach developed for the microscale modelling of particles which undergo large deformations is presented. The proposed method is based on the bonded-particle model (BPM) and multi-stage strategy to adjust material and model parameters. By the BPM, modelled objects are represented as agglomerates which consist of smaller ideally spherical particles and are connected with cylindrical solid bonds. Each bond is considered as a separate object and in each time step the forces and moments acting in them are calculated. The developed approach has been applied to simulate the compaction of elastomeric rubber particles as single particles or in a random packing. To describe the complex mechanical behaviour of the particles, the solid bonds were modelled as ideally elastic beams. The functional parameters of solid bonds as well as material parameters of bonds and primary particles were estimated based on the experimental data for rubber spheres. Obtained results for acting force and for particle deformations during uniaxial compression are in good agreement with experimental data at higher strains