Approaching the catalytic mechanism of protein lysine methyltransferases by biochemical and simulation techniques.

Protein lysine methyltransferases (PKMTs) transfer up to three methyl groups to the side chains of lysine residues in proteins and fulfill important regulatory functions by controlling protein stability, localization and protein/protein interactions. The methylation reactions are highly regulated, and aberrant methylation of proteins is associated with several types of diseases including neurologic disorders, cardiovascular diseases, and various types of cancer. This review describes novel insights into the catalytic machinery of various PKMTs achieved by the combined application of biochemical experiments and simulation approaches during the last years, focusing on clinically relevant and well-studied enzymes of this group like DOT1L, SMYD1-3, SET7/9, G9a/GLP, SETD2, SUV420H2, NSD1/2, different MLLs and EZH2. Biochemical experiments have unraveled many mechanistic features of PKMTs concerning their substrate and product specificity, processivity and the effects of somatic mutations observed in PKMTs in cancer cells. Structural data additionally provided information about the substrate recognition, enzyme-substrate complex formation, and allowed for simulations of the substrate peptide interaction and mechanism of PKMTs with atomistic resolution by molecular dynamics and hybrid quantum mechanics/molecular mechanics methods. These simulation technologies uncovered important mechanistic details of the PKMT reaction mechanism including the processes responsible for the deprotonation of the target lysine residue, essential conformational changes of the PKMT upon substrate binding, but also rationalized regulatory principles like PKMT autoinhibition. Further developments are discussed that could bring us closer to a mechanistic understanding of catalysis of this important class of enzymes in the near future. The results described here illustrate the power of the investigation of enzyme mechanisms by the combined application of biochemical experiments and simulation technologies.

Enhancing Cutting Efficiency and Minimizing Forces for Nomex Honeycomb Core Using Grey Relational Analysis and Desirability Function Analysis.

Nomex Honeycomb core is the foundational building block for manufacturing aerospace composite components. Its usage requires machining honeycomb in complex aerodynamic profiles where the quality of the core is governed by accuracy and precision of cut profiles. The assessment of accuracy and precision is directly related to forces induced in the cutting tool and cutting efficiency. These two parameters form the basis of a multi-objective function that this paper aims to optimize for the milling operation. The parameter of depth of cut considered in this paper has not been analyzed in a multi-objective optimization study of the Nomex Honeycomb core previously. A Taguchi-based array of Design of Experiments followed by Analysis of Variance and correlation analysis is utilised. The results indicate that the most significant factor is the feed rate, with a percentage contribution of 72% for the cutting forces and depth of cut, with a percentage contribution of 85% in the case of cutting efficiency. The two parameters are optimized using Desirability Function Analysis and Grey Relational Analysis. The results are validated through experimental runs with an error within 5% of the statistical predictions, with the percentage improvement in cutting forces for optimum runs as compared to the worst experimental run at 47.8%. The percentage improvement in cutting efficiency likewise is 11%.

The Influence of Syringic Acid and Erucic Acid on the Antioxidant Properties of Natural Rubber: Experimental and Molecular Simulation Investigations.

In this work, the influence of syringic acid (SA) and erucic acid (EA) on the oxidation resistance of natural rubber (NR) was investigated by combining experimental and computational methods. The antioxidant activities of SA and EA were predicted by calculating the enthalpy of bond dissociation (BDE), the anti-migration ability of antioxidants (AOs) in the rubber matrix by calculating the mean square displacement (MSD), and the effect of antioxidants on oxygen barrier properties of rubber materials by calculating the permeability coefficient (P). The predicted result is that EA has a better comprehensive performance than SA. The DPPH (2,2-diphenyl-1-picrylhydrazyl) test and mechanical properties test demonstrated the results predicted by the simulations. Both SA and EA can protect natural rubber, while EA has a better comprehensive effect.

Bio-Inspired High Sensitivity of Moisture-Mechanical GO Films with Period-Gradient Structures.

Moisture actuators can accomplish humidity-triggered energy-conversion process, through material screening and structural design. Inspired by natural caterpillars and the hydrophilic properties of graphene oxide (GO), this work proposes a geometrical design of period-gradient structures in GO films for fabricating moisture actuators. These novel period-gradient-structured GO films exhibit excellent dynamic performance that they could deform at 1000° with a small radius in several seconds at a high relative humidity (RH ≈ 80%). The properties of fast actuating speed and high response to deformation are achieved through the structural designing of the sole GO film by a one-step formation process. A mechanics-based theoretical model combined with the finite element simulation is presented to demonstrate the actuating mechanism in geometry, moisture, and mechanics, which lays the foundation for potential applications of GO films in remote control, environmental monitoring, and man-machine interactions.

Cellulose crystals plastify by localized shear.

Cellulose microfibrils are the principal structural building blocks of wood and plants. Their crystalline domains provide outstanding mechanical properties. Cellulose microfibrils have thus a remarkable potential as eco-friendly fibrous reinforcements for structural engineered materials. However, the elastoplastic properties of cellulose crystals remain poorly understood. Here, we use atomistic simulations to determine the plastic shear resistance of cellulose crystals and analyze the underpinning atomic deformation mechanisms. In particular, we demonstrate how the complex and adaptable atomic structure of crystalline cellulose controls its anisotropic elastoplastic behavior. For perfect crystals, we show that shear occurs through localized bands along with noticeable dilatancy. Depending on the shear direction, not only noncovalent interactions between cellulose chains but also local deformations, translations, and rotations of the cellulose macromolecules contribute to the response of the crystal. We also reveal the marked effect of crystalline defects like dislocations, which decrease both the yield strength and the dilatancy, in a way analogous to that of metallic crystals.