ABSTRACT This present study investigates the mechanical and deformation behaviour of pristine and carbon nanotube (CNT)-reinforced AlCoCrFeNi high-entropy alloys (HEAs) using molecular dynamics (MD) simulations. The results reveal that an increase in the atomic fraction of Al in pristine AlCoCrFeNi HEAs leads to reduced mechanical behaviour. The mechanical behaviour of the pristine AlCoCrFeNi HEAs notably improves following CNT reinforcement, particularly when using CNT with higher chirality. As the chirality of the CNT increases from (6,6) to (15,15), Young's modulus, yield stress, and toughness of the (15,15) CNT-Al20CoCrFeNi HEA enhance by 17.34%, 29.44%, and 44.44% compared to the (6,6) CNT – Al20CoCrFeNi HEA. HEAs with lower Al fractions experience more substantial stress drops due to rapid structural changes. CNT reinforcement, particularly with higher chirality, decelerates this structural transformation, enhancing yield strength greatly. The analysis of the dislocation evolution revealed that the CNT-reinforced HEA exhibits higher dislocation density compared to the pristine HEA, indicating strain hardening from CNT reinforcement. Furthermore, examination of atomic shear strain reveals confined deformation along shear bands in CNT-reinforced HEAs, leading to the deformation and eventual fracture of CNTs. This study provides valuable insights for enhancing the mechanical behaviour of CNT-reinforced AlCoCrFeNi HEAs, aiding in their design and development.

ABSTRACT Nanotwinned exist in crystals as coherent interfaces with low interfacial energy, which can not only improve the strength of metal materials, but also increase the ductility. In this manuscript, we have performed molecular dynamics simulations of the mechanical properties of a nano-columnar crystalline Cu-Ni alloy with different twin boundary spacing. It is found that the model without twin has a stacking fault tetrahedron composed of stair-rod dislocations, which results in a small change in dislocation density at the later stage of deformation, and the average stress after yielding is lower than that of the model with twin. During the deformation process, with the increase of Other atoms, the dislocation slip barrier is enhanced, the tensile strength is increased, and the yield phenomenon is delayed, which is more obvious with the decrease of twin boundary spacing. The dislocation density decreases with the decrease of the spacing of the twin boundary, and the dislocation segments become shorter. When the twin boundary spacing is 0.625 nm, the tensile strength is increased by about 71% compared with the model without twin structure.

ABSTRACT The tensile deformation behaviour of blended polyethylene (PE) was studied using molecular dynamic methods. The blended PE was modeled by blending linear chains with different molecular weights based on a united atom model. The mechanical response and microscopic conformational behaviours of blended PE were investigated at different strain rates and temperatures. The interatomic energy evolution displayed a similar trend to the stress–strain curve showing the stiffness of blended PE increase with a higher fraction of chain with high molecular weight. The microstructure metrics associated with free volume, orientation, entanglement and crystallisation were recorded as a function of strain in detail to obtain insight into the role of PE chains with different molecular weights for blended PE during deformation. The conformation evolution indicates that orientation and disentanglement are more noticeable in the short chain with low molecular weight in a blended PE system, while the long chain promotes the crystallisation of the initial chain structure. The chain entanglement evolution clearly shows some new flexion nodes created to entangle short chains again, implying that re-entanglement might exist during the tensile deformation.

ABSTRACT Size plays an important role on the deformation mechanism of nanopillars. With decreasing size, many FCC nanopillars exhibit dislocation starvation which is responsible for their high strength. However, many details about the dislocation starvation like how often it occurs, and how much is its contribution to the total plastic strain, are still elusive. Similarly, the size below which the dislocation starvation occurs is not clearly established. In this context, atomistic simulations have been performed on the compression of <110> Cu nanopillars with size (d) ranging from 5 to 21.5 nm. Molecular dynamics (MD) simulation results indicate that the nanopillars deform by the slip of extended dislocations and exhibit dislocation starvation mainly at small sizes (<20 nm). The frequency of the occurrence of dislocation starvation is highest in small-sized nanowires and it decreases with increasing size. Above the size of 20 nm, no dislocation starvation has been observed. Furthermore, we define the dislocation starvation strain and based on this, it has been shown that the contribution of the dislocation starvation to the total plastic strain decreases from 70% in small-sized nanopillars to below 5% in large-sized pillars. The present results suggest that dislocation starvation is a dominant phenomenon in small-sized nanopillars.

ABSTRACT In this work, molecular docking and molecular dynamics (MD) simulation were applied to investigate the ability of natural cyclodextrins (CDs; Alpha, Beta and Gamma Cyclodextrins) and modified CDs (hydroxypropyl, random methyl and amino Beta Cyclodextrins) to form the stable inclusion complexes (ICs) with Crizotinib, the oral small molecule kinase inhibitor as a chemotropic drug. Results of molecular docking and MD simulation studies demonstrated that Crizotinib forms stable ICs with all natural and modified CDs and in the presence of this drug, all six CDs become more rigid. The presence of Crizotinib and the release of water molecules result in a decrease in the number of hydrogen bonds between cyclodextrins (CDs) and solvent molecules within the encapsulated CDs, compared to the hydrogen bonds observed in free CDs. Additionally, HPBCD exhibited the strongest affinity for binding and established the highest quantity of hydrogen bonds with Crizotinib. Finally, all results of this paper demonstrated the potential of using this formulation to improve the bioavailability of the selected drug.

ABSTRACT In many studies published in recent years, corrosion scientists proved that various drug molecules can exhibit high inhibition performance against the corrosion of metal surfaces and alloys. This study presents the adsorption behaviour and inhibition mechanism of Omeprazole and Tinidazole on steel surface in gas phase and aqueous acidic conditions using quantum chemical calculations and molecular dynamics simulations. Well-known quantum chemical parameters such as EHOMO, ELUMO, energy gaps, dipole moment, global hardness, softness, electrophilicity, electrodonating power, electroaccepting power and the fraction of electron transfer, were calculated to understand the corrosion inhibition properties and interactions with the steel surface of the studied molecules. Fukui indices analysis was performed to identify the local reactivities of the molecules. Additionally, Monte Carlo simulations were used to determine the optimal adsorption configuration of the inhibitors onto a Fe (1 1 0) surface. The study's findings provide valuable insights into preventing corrosion of steel surfaces in aqueous acidic environments. The theoretical data obtained was evaluated in terms of Maximum Hardness, Minimum Polarizability and Minimum Electrophilicity Principles.

ABSTRACT Microtubulin is an important research target for anti-tumour drugs, which can be used to inhibit microtubulin polymerisation and improve the efficacy of tumour therapy. In this paper, 61 microtubule protein inhibitors with anticancer activity are selected as the data set for building a stable and effective QSAR (Topomer CoMFA) model, resulting in a Topomer CoMFA model with validation coefficients of  = 0.737 and  = 0.922. Fifteen new inhibitors with theoretically high activity are designed by screening the zinc database for new fragments with good activity through the contribution descriptors obtained by Topomer CoMFA. After simulating the binding affinity and interaction of the inhibitors with the proteins by molecular docking, all these compounds formed strong interactions such as hydrogen bonds with multiple amino acids in the receptor proteins. Furthermore, molecular dynamics results show that the predicted highly active compounds exhibited stable and favourable binding patterns to the active pocket. In addition, these new compounds exhibit good ADMET properties. The present work establishes a reliable QSAR model for computational simulation screening of microtubulin drug development and provides a basis for further access to novel microtubulin inhibitors.

ABSTRACT The use of FDA-approved drugs for the therapy of lung cancer through drug repurposing is a noteworthy approach. We retrieved all the FDA-approved triazole-based drugs from Drugbank and conducted docking-based virtual screening of the triazole-based FDA-approved drugs against the EGFR target. Deferasirox demonstrated hydrogen bonding interactions with residues Thr 830, Asp 831, Lys 721 and Met 769 of the EGFR-TKD receptor (PDB ID: 1M17) and Posaconazole showed hydrogen bonding with residues Met 769 and Glu 734 of the similar EGFR receptor along with the binding energies of −9.60, −9.50, kcal/mol respectively. The dock score for reference molecule found to be −6.70 (kcal/mol). Best two ligands (Deferasirox and Posaconazole) were selected on the basis of dock score from the virtual screening results for in vitro NRU assay using A549 cells to determine their cytotoxicity and cell viability. During the in vitro NRU experiment, Deferasirox and Posaconazole demonstrated IC50 values of 114.9 and 910.2 µM, respectively. MD simulations were performed to investigate the dynamic behaviour and stability, and interactions were compared to the standard inhibitor for the EGFR target. DFT studies were carried out to determine their molecular properties, including their electronic structure, bond lengths and bond energies. The results of the in silico and in vitro studies were analysed to assess the potential of Deferasirox and Posaconazole for use as anticancer agents in the mitigation of lung cancer symptoms. This study focused on repurposing FDA-approved triazole-based compounds to identify their potential as effective lung cancer treatments with anticancer properties.

ABSTRACT Glucokinase (GK, EC 2.7.1.2) is a crucial enzyme that catalyses the conversion of glucose to glucose-6-phosphate. It is used to treat type-2 diabetes (T2D), a serious metabolic disorder that is still at the forefront without proper medication. Fast Rigid Exhaustive Docking (FRED) was carried out for 400,000 compounds from the Zinc database to identify novel glucokinase activators. The hit compounds ZINC69775727, ZINC9114647, ZINC91773667, ZINC9305321, and ZINC96165848 interacted strongly with allosteric site residues and, formed hydrogen bonds with ARG 63. The hit compounds met the criterion for drug-likeness, according to the ADME prediction. The compounds were then subjected to 100 ns of molecular dynamics simulation and MM-GBSA calculation using DESMOND. The findings demonstrated that the compounds had good stability and minimal fluctuation throughout the course of the simulation, pointing to the potential of the chosen compounds for glucokinase activation. The compound ZINC69775727 in particular has the lowest binding energy of −111.1 kcal/mol, which is lower than the native ligand’s binding energy of −102.84 kcal/mol and the binding energies of the control compounds PSN-GK1 and Piragliatin, which are −102.49 kcal/mol and −107.767 kcal/mol, respectively. Therefore, the information from this work may be useful in finding novel small molecules as GKAs.

ABSTRACT To explore the mechanical properties and deformation mechanism of twin γ-TiAl alloy under load and impact, based on the special interface structure in polycrystals, twinning at room temperature is established in this paper simulation of nanoindentation response of twin γ-TiAl alloy. Through the load-displacement curve, the hardness and Young's modulus of the workpiece are obtained. By analysing the microstructure evolution behaviour under the action of the indenter, it is found that during the loading process, multiple dislocation rings are generated in the grain and slip to the lower part of the workpiece, resulting in the hardness decreasing with the increase of the indentation depth, which is consistent with the indentation size effect; The dislocation lock generated during the unloading process delayed the annihilation of the defect structure, but the dislocation and stacking fault structure disappeared completely and the stress concentrated at the defect residue; in the stress relaxation stage, the dislocation ring structure in the grain extends and annihilates away from the grain boundary, releasing a large amount of stress to reduce the indentation load, and then the defect structure around the indenter is stable to keep the load stable, with high stress at the defect.