The traditional computational modeling of protein structure, dynamics, and interactions remains difficult for many protein systems. It is mostly due to the size of protein conformational spaces and required simulation time scales that are still too large to be studied in atomistic detail. Lowering the level of protein representation from all-atom to coarse-grained opens up new possibilities for studying protein systems. In this review we provide an overview of coarse-grained models focusing on their design, including choices of representation, models of energy functions, sampling of conformational space, and applications in the modeling of protein structure, dynamics, and interactions. A more detailed description is given for applications of coarse-grained models suitable for efficient combinations with all-atom simulations in multiscale modeling strategies.

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Coarse-Grained Protein Models and Their Applications

Monomolecular arrays of protein or glycoprotein subunits forming surface layers (S-layers) are one of the most commonly observed prokaryotic cell envelope components. S-layers are generally the most abundantly expressed proteins, have been observed in species of nearly every taxonomical group of walled bacteria, and represent an almost universal feature of archaeal envelopes. The isoporous lattices completely covering the cell surface provide organisms with various selection advantages including functioning as protective coats, molecular sieves and ion traps, as structures involved in surface recognition and cell adhesion, and as antifouling layers. S-layers are also identified to contribute to virulence when present as a structural component of pathogens. In Archaea, most of which possess S-layers as exclusive wall component, they are involved in determining cell shape and cell division. Studies on structure, chemistry, genetics, assembly, function, and evolutionary relationship of S-layers revealed considerable application potential in (nano)biotechnology, biomimetics, biomedicine, and synthetic biology.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1111/1574-6976.12063

S-layers: principles and applications

Innovative honeycomb-based structures have been paid substantial attention in recent years due to their superb mechanical performances and specific functions. The presented study made acomprehensive overview on the development of the innovative honeycomb-based structures in the past two decades, including filled-type, embedded, tandem, hierarchical, auxetics with Negative Poisson's Ratio (NPR), etc. Mechanical performances of these structures were commented with advantages and disadvantages, related on their geometric configurations, mechanical performance and dynamic response, respectively. The challenges as well as future directions were also analyzed. The achievements provide significant guidelines in designing of new generation light-weight honeycomb-based structures.

Recent advances in novel metallic honeycomb structure

In plants, there is a large overlap between cold and circadian regulated genes and in Arabidopsis, we have shown that cold (4°C) affects the expression of clock oscillator genes. However, a broader insight into the significance of diurnal and/or circadian regulation of cold responses, particularly for metabolic pathways, and their physiological relevance is lacking. Here, we performed an integrated analysis of transcripts and primary metabolites using microarrays and gas chromatography-mass spectrometry. As expected, expression of diurnally regulated genes was massively affected during cold acclimation. Our data indicate that disruption of clock function at the transcriptional level extends to metabolic regulation. About 80% of metabolites that showed diurnal cycles maintained these during cold treatment. In particular, maltose content showed a massive night-specific increase in the cold. However, under free-running conditions, maltose was the only metabolite that maintained any oscillations in the cold. Furthermore, although starch accumulates during cold acclimation we show it is still degraded at night, indicating significance beyond the previously demonstrated role of maltose and starch breakdown in the initial phase of cold acclimation. Levels of some conventional cold induced metabolites, such as γ-aminobutyric acid, galactinol, raffinose and putrescine, exhibited diurnal and circadian oscillations and transcripts encoding their biosynthetic enzymes often also cycled and preceded their cold-induction, in agreement with transcriptional regulation. However, the accumulation of other cold-responsive metabolites, for instance homoserine, methionine and maltose, did not have consistent transcriptional regulation, implying that metabolic reconfiguration involves complex transcriptional and post-transcriptional mechanisms. These data demonstrate the importance of understanding cold acclimation in the correct day-night context, and are further supported by our demonstration of impaired cold acclimation in a circadian mutant.

/pdf/interaction-with-diurnal-and-circadian-regulation-results-in-10pqbh9j2c.pdf

Interaction with Diurnal and Circadian Regulation Results in Dynamic Metabolic and Transcriptional Changes during Cold Acclimation in Arabidopsis

Gene electrotransfer is a powerful method of DNA delivery offering several medical applications, among the most promising of which are DNA vaccination and gene therapy for cancer treatment. Electroporation entails the application of electric fields to cells which then experience a local and transient change of membrane permeability. Although gene electrotransfer has been extensively studied in in vitro and in vivo environments, the mechanisms by which DNA enters and navigates through cells are not fully understood. Here we present a comprehensive review of the body of knowledge concerning gene electrotransfer that has been accumulated over the last three decades. For that purpose, after briefly reviewing the medical applications that gene electrotransfer can provide, we outline membrane electropermeabilization, a key process for the delivery of DNA and smaller molecules. Since gene electrotransfer is a multipart process, we proceed our review in describing step by step our current understanding, with particular emphasis on DNA internalization and intracellular trafficking. Finally, we turn our attention to in vivo testing and methodology for gene electrotransfer.

/pdf/gene-electrotransfer-a-mechanistic-perspective-2dsjsa1bhd.pdf

Gene Electrotransfer: A Mechanistic Perspective

Advances in Planar Lipid Bilayers and Liposomes

Toughening in nanosilica-reinforced epoxy with tunable filler-matrix interface properties

In multiscale molecular dynamics simulations the accuracy of detailed models is combined with the efficiency of a reduced representation. For several applications - namely those of sampling enhancement - it is desirable to combine fine-grained (FG) and coarse-grained (CG) approaches into a single hybrid approach with an adjustable mixing parameter. We present a benchmark of three algorithms that use a mixing of the two representation layers using a Lagrangian formalism. The three algorithms use three different approaches for keeping the particles at the FG level of representation together: 1) addition of forces, 2) mass scaling, and 3) temperature scaling. The benchmark is applied to liquid hexadecane and includes an evaluation of the average configurational entropy of the FG and CG subsystems. The temperature-scaling scheme achieved a 3-fold sampling speedup with little deviation of FG properties. The addition-of-forces scheme kept FG properties the best but provided little sampling speedup. The mass-scaling scheme yielded a 5-fold speedup but deviated the most from FG properties.

/pdf/benchmark-of-schemes-for-multiscale-molecular-dynamics-4dpke30tkl.pdf

Benchmark of Schemes for Multiscale Molecular Dynamics Simulations

\nThis paper presents a study undertaken following the collaboration between specialists in two multidisciplinary fields, namely engineering and medicine. It was aimed at solving a practical problem by developing of a handle for use in orthopedic surgery. Specific engineering tools, knowledge and processes and methods were used for accomplishing this task. Tailoring devices according to surgeons preferences for ensuring an ergonomic use is an important criterion alongside functional and sterilization requirements, cost and fabrication time, 3D printing representing a feasible manufacturing solution as this research proves. The article details the steps required to complete the final product: design and redesign, numerical analysis, prototypes manufacturing and testing. To perform the numerical analysis that highlights the device mechanical behavior, finite element method was used in assessing different handle designs.\n

/pdf/development-and-3d-printing-of-an-abs-ergonomic-handle-for-4sv9ytmts5.pdf

Development and 3D Printing of an ABS Ergonomic Handle for Medical Use A case study

This paper presents some modelling techniques useful for the optimisation of numerical models of vehicle interior parts in terms of improving the structural response in impact applications. A procedure regarding the random distribution of thickness of the elements for a selected area within a user-specified tolerance is presented. Procedures implemented in a custom-written code and the algorithms used for the random distribution are also presented. This was required because the parts presented some deviations from the nominal value (of thickness), probably due to the manufacturing process. With experiments performed with equipment constructed according to ECE R21 regulation, the results obtained using three numerical models are compared and solutions for numerical modelling are presented. Results (accelerations: maximum, average, at peaks; time: peak time, time interval between two peaks; coefficient of restitution) obtained using the numerical models were evaluated and compared with the experimental data.

Anton Hadar

Papers

Advances in Planar Lipid Bilayers and Liposomes

Toughening in nanosilica-reinforced epoxy with tunable filler-matrix interface properties

Benchmark of Schemes for Multiscale Molecular Dynamics Simulations

Development and 3D Printing of an ABS Ergonomic Handle for Medical Use A case study

Computational modelling of vehicle interior components for impact applications: Thickness analysis