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• Essential genes (Pyridoxal kinase and sterol alpha-14 demethylase) are drug targets. • Discerned the atomistic interactions of small molecules with target proteins through Molecular Docking and MD Simulations. • Non-bonded contacts and MM-PBSA calculations aided in deciphering nitazoxanide and artemisinin dynamic interactions with the target proteins. • This biocomputing study identified plausible drug inhibitors against essential leishmanial genes. Leishmania donovani , an obligatory intracellular flagellate pathogen, is the underlying cause of visceral leishmaniasis (VL), a fatal disease that poses a significant challenge to existing therapeutic approaches and leads to human mortality. In an endeavor to find an antileishmanial drug to combat VL, we aimed to assess the approved drug molecules against the specific drug targets of VL. In this study, a theoretical method was used to select two essential therapeutic targets (pyridoxal kinase [PK] and sterol alpha-14 demethylase [SDM]) which were present in both the data set of essential genes and drug target proteins. The selected PK and SDM proteins in L. donovani play pivotal roles as essential enzymes in the crucial vitamin B6 salvage and sterol biosynthesis pathways, respectively, leading to pathogenicity in humans. In addition to that drugs were gathered from the DrugBank and Drug Central databases and 325 (out of 4867) compounds having anti-parasitic properties were screened by PASS analysis. Consequently, three ligands (referred to as Lig_1, Lig_2, and Lig_3) were chosen based on their elevated Pa values, docking scores, and notable medicinal applications. Moreover, the result obtained from MD simulation suggests Lig_1 [Nitazoxanide (PubChem ID-41684)] does not affect the structural integrity of both targets. Additionally, evaluation of total binding energies by MMPBSA analysis showed stronger binding of Lig_1 with PK and SDM is -100.71 and -175.61 kJ/mol, respectively compared to others. As a whole, the methodology employed in this research involves the simultaneous identification of suitable protein targets and potential inhibitors. Through this investigation, we have demonstrated that compounds derived from a biocomputing approach exhibit interaction mechanisms as inhibitors against drug targets, offering a promising avenue for addressing VL. [ABSTRACT FROM AUTHOR]

In this paper, experimental work is supported by multi-scale numerical modeling to investigate nanomechanical response of pristine and ion irradiated with Fe2＋ ions with energy 5 MeV high purity iron specimens by nanoindentation and Electron Backscatter Diffraction. The appearance of a sudden displacement burst that is observed during the loading process in the load–displacement curves is connected with increased shear stress in a small subsurface volume due to dislocation slip activation and mobilization of pre-existing dislocations by irradiation. The molecular dynamics (MD) and 3D-discrete dislocation dynamics (3D-DDD) simulations are applied to model geometrically necessary dislocations (GNDs) nucleation mechanisms at early stages of nanoindentation test; providing an insight to the mechanical response of the material and its plastic instability and are in a qualitative agreement with GNDs density mapping images. Finally, we noted that dislocations and defects nucleated are responsible the material hardness increase, as observed in recorded load–displacement curves and pop-ins analysis. [ABSTRACT FROM AUTHOR]

Microtubule-affinity regulating kinase 4 (MARK4) is linked with the development of cancer, diabetes and neurodegenerative diseases. Due to its direct role in the hyperphosphorylation of tau protein, MARK4 is considered as an attractive target to fight Alzheimer's disease (AD) and neuroinflammation. In the present study, we have selected Harmaline (HAR), an alkaloid of Paganum harmala , to investigate its MARK4 inhibitory potential and its binding mechanism. Molecular docking and fluorescence binding studies were carried out to estimate the binding affinity of the HAR with the MARK4. We observed an excellent binding affinity of HAR to the MARK4 (K = 107 M−1), further complemented by isothermal titration calorimetric measurements. In addition, HAR significantly inhibits the kinase activity of MARK4 (IC 50 value of 4.46 μM). Structural investigations suggested that HAR binds to the active site pocket and forms several non-covalent interactions with biologically important residues of MARK4. All-atom molecular dynamics simulation studies further advocated that the MARK4-HAR complex is stabilized throughout the trajectory of 200 ns and causes a little conformational change. All these findings suggest that HAR is a potential MARK4 inhibitor that can be implicated in managing MARK4-associated diseases, including AD. • Hyperphosphorylation of tau protein by MARK4 is a critical event in the pathogenesis of Alzheimer's disease. • Inhibiting MARK4 by Harmaline may be implicated in therapeutic management of Alzheimer's disease. • Docking and MD simulation studies suggested the formation of a stable complex of MARK4 and Harmaline. • Fluorescence and ITC measurements further revealed strong binding affinity of Harmaline for MARK4. • Harmaline inhibits the kinase activity of MARK4 and thus control hyperphosphorylation of tau protein. [ABSTRACT FROM AUTHOR]

[Display omitted] • A graded hexagonal boron-nitride/graphene sheet with an atomic content gradient can be an intrinsic and robust antifouling coating material. • The antifouling mechanism is attributed to the gradient in van der Waals potential induced by the gradient in carbon content. • The antifouling mechanism is robust in various conditions including at high temperatures, with few atomic defects, and for both solid and liquid contaminations. Although considerable efforts have been made in various fields for surface cleaning, keeping solid surfaces from nanoscale contamination remains extremely challenging. It is demonstrated here, based on molecular dynamics simulations, that graded hexagonal boron-nitride/graphene (h -BNC) can be an intrinsic and robust antifouling coating material. It is shown that nanoobjects in both solid and liquid forms can move spontaneously on the graded h -BNC toward the direction of decreasing carbon content. The driving mechanism is attributed to the gradient in van der Waals potential induced by the gradient in carbon content. The graded structure of graded h -BNC allows for its use in robust nanoscale surface cleaning and offers new opportunities for the development of antifouling coatings. [ABSTRACT FROM AUTHOR]

· A new series of new thiadiazol derivatives has been designed and synthesized as VEGFR-2 inhibitors. · VEGFR-2 inhibitory activity and cytotoxic effect were assessed. · The effect on cell cycle and apoptosis was determined. · In silico docking, MD simulation, ADMET, and toxicity studies were carried out. The presented study reports the synthesis, in silico and in vitro evaluations of a series of novel thiadiazole derivatives designed with the pharmacophoric features of Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) inhibitors. A comprehensive assessment against MCF-7 and HepG2 cancer cell lines revealed promising inhibitors, particularly, N -(4-((E)-1-(((Z)-5-acetyl-3-(2-chlorophenyl)-1,3,4-thiadiazol-2(3 H)-ylidene) hydrazono) ethyl) phenyl)-4-chlorobenzamide (compound 22) exhibited a significantly low half-maximal inhibitory concentration (IC 50) value against both MCF-7 and HepG2 cells of 0.03 µM and 0.39 µM, respectively. The rest of compounds exhibited also significant IC 50 values against MCF-7 and HepG2 cells of (0.07–4.7 µM) and (0.12–8.75 µM), respectively. Furthermore, compound 22 displayed a VEGFR-2 inhibitory activity (VEGFR-2 = 0.042 µM) comparable to the established inhibitor sorafenib (VEGFR-2 = 0.041 µM). Detailed cell cycle analysis demonstrated that compound 22 induced a G0-G1 phase arrest of the MCF-7 cells (71.33 %), indicative of its potential to modulate cell cycle progression. Notably, compound 22 also exhibited a substantial increase in apoptosis in the MCF-7 cells, particularly in early (22.04 %) and late stages (13.94 %), underscoring its remarkable pro-apoptotic effect. Additionally, Compound 22 demonstrated a notable decrease in the migratory ability and wound healing capacity of MCF-7 cells. Computational studies, including molecular docking, revealed high binding affinities. Over a 200 ns MD simulation, the VEGFR-2-compound 22 complex initially displayed a rapid increase in RMSD followed by stability around 3.5 Å due to ligand conformational change while maintaining stable protein binding. This was confirmed by RMSF, SASA, RoG, and hydrogen bonding analysis. MM-GBSA, ProLIF, PCAT and FEL studies confirmed VEGFR-2-compound 22 complex binding at both dynamic and energetic levels. The computational ADMET studies demonstrated favorable pharmacokinetic properties. Furthermore, Density Functional Theory (DFT) studies confirmed the reactivity and stability of compound 22. These comprehensive findings underscore the potential of compound 22 as a lead candidate for further investigation in the development of VEGFR-2-targeted anticancer agents. [Display omitted] [ABSTRACT FROM AUTHOR]

This study analyzed the metabolite profiles and antioxidant capacities of two waxy and non-waxy Korean red rice accessions newly bred. Fifteen phenolic compounds were detected in the rice samples. Accession1 had high fatty acids, phytosterols, and vitamin E; accession3 had high vitamin E and phytosterol; and accession4 had a high total flavonoid. The correlation analysis findings from this study validated the positive association between all the metabolites and antioxidant activity. in silico results revealed that protocatechuic acid had a docking score of −9.541, followed by luteolin, quercetin, and caffeic acid, all of which had significant docking scores and a significant number of contacts. Similarly, molecular dynamics simulations showed that phytochemicals had root mean square deviation values of <2.8 Å with Keap 1, indicating better stability. This study provides valuable insights into potential directions for future investigations and improvements in the functional qualities of other colored rice varieties. [Display omitted] • Comparison and analysis of the metabolite profiles of two red rice varieties. • accession 1 (Acc1) had a high content of fatty acids, phytosterols, and vitamin E. • Acc3 had a high content of vitamin E and phytosterol. • Acc4 had a high total flavonoid content. • Docking molecules exhibited consistent RMSD values of <2.8 Å over 100 ns. [ABSTRACT FROM AUTHOR]

• Novel substituted chalcones tethered 1,3,5-triazine hybrids were designed and developed with high purity and good yield. • All novel chalcone-1,3,5-triazine hybrid molecules (5a-j) displayed excellent anticancer activity towards PC3, A549, MCF7 and Colo 205 cancer cell lines. • The experimental results were best supported by molecular docking, MD simulations, and DFT studies. • The apoptotic mechanism in anticancer activity was further confirmed by nuclear staining analysis i.e. DAPI analysis. • ADME analysis results indicates the human oral absorption is greater than 75 %. A novel library of chalcone tethered 1,3,5-triazine hybrids (5a-j) were designed and synthesized and their structures were confirmed by using spectroscopic/analytical techniques. The anticancer activity of the synthesized novel derivatives (5a-j) was evaluated against four human cancer cell lines: PC3 (Prostate cancer), A549 (Lung cancer), MCF7 (Breast cancer), and Colo-205 (Colon cancer) by employing of MTT assay method. In comparison to "Etoposide", all the compounds showed excellent to moderate activity. The IC 50 values of the novel derivatives (5a-j) ranged from 0.01±0.0032 µM to 12.4 ± 6.18 µM whereas positive control (Etoposide) showed 0.14±0.017 µM to 3.08±0.135 µM respectively. The newly developed substituted chalcone linked triazine hybrids were found to be good alternative anticancer agents. Among the all, (5a-j), mainly 5a, 5e, 5f, 5 g and 5j displayed highly potent anticancer activity towards MCF7 (5a), A549 (5 g), PC3 (5e, 5f) and Colo-205 (5j) human cancer cell lines. Principally, two compounds 5a and 5e were displayed as the most promising activities. The apoptotic mechanism in anticancer activity was further confirmed by nuclear staining analysis on more active test compounds 5a and 5e by DAPI (4′,6-diamidino-2-phenylindole) at different concentrations with MCF-7 cells, Additionally, all the synthesized compounds were investigated by molecular docking simulation studies with topoisomerase-IIβ enzyme (PDB ID: 3QX3) protein to correlate the in-vitro biological activity data evaluated on four human cancer cell lines. The docking scores of the newly produced conjugates (5a-j) varied from – 7.52 kcal/mol to -6.27 kcal/mol, indicating these compounds serve as an inhibitor. Human oral absorption is expected to be greater than 75 %. The in-vitro cytotoxicity behavior of tested compounds was further supported by in-silico predictions such as ADME, MD simulations and DFT studies. In-vitro cytotoxicity activity of newly developed substituted chalcones tethered 1,3,5-triazine hybrids towards four human cancer cell lines: PC3 (Prostate cancer), A549 (Lung cancer), MCF7 (Breast cancer), and Colo-205 (Colon cancer) was evaluated by employing of MTT assay method. In comparison to "Etoposide", all the compounds showed excellent to moderate activity. The IC 50 values of the novel derivatives (5a-j) ranged from 0.01±0.0032 µM to 12.4 ± 6.18 µM whereas positive control (Etoposide) showed 0.14±0.017 µM to 3.08±0.135 µM respectively. The newly developed substituted chalcone linked triazine hybrids were found to be good alternative anticancer agents. The experimental observations were further supported by molecular docking, MD simulations, DFT studies, DAPI and ADME analyses. [Display omitted] [ABSTRACT FROM AUTHOR]

Twin boundary (TB) migration, facilitated by the motion of disconnections, plays a pivotal role in the deformation of body-centered cubic (BCC) crystals. Comprehending the migration rules of twinning disconnections (TDs) under shear stress is significant in elucidating the role of twin migration in BCC plasticity. Nevertheless, our understanding of the atomic structure and migration mechanics of TDs remains incomplete. In this study, we employ the theory of interfacial defects and molecular dynamics (MD) simulations to thoroughly investigate potential { 112 } [ 111 ] TDs in BCC tantalum (Ta). These TDs are characterized by their Burgers vectors, which were predicted through related dichromatic pattern analysis. We reveal that single-layer and double-layer TDs represent the fundamental building blocks (units) of multi-layer TDs. Their migration directions are entirely opposite under the same shear loading, and they cannot annihilate each other when they migrate "face to face". Furthermore, these migration rules governing single-layer and double-layer TDs offer a comprehensive explanation for the complex composition and decomposition patterns observed among various multi-layer TDs. What's more, we demonstrated that TDs with zero Burgers vector can only be driven as a whole under coupled loading conditions. These findings significantly enhance our understanding of TB migrations in BCC metals. [Display omitted] [ABSTRACT FROM AUTHOR]

The 5-Hydroxytryptamine (5HT)-2A receptor, a key target in psychoactive drug development, presents significant challenges in the design of selective compounds. Here, we describe the construction, evaluation and validation of two machine learning (ML) models for the classification of bioactivity mechanisms against the (5HT)-2A receptor. Employing neural networks and XGBoost models, we achieved an overall accuracy of around 87 %, which was further enhanced through molecular modelling (MM) (e.g. molecular dynamics simulations) and binding free energy analysis. This ML-MM integration provided insights into the mechanisms of direct modulators and prodrugs. A significant outcome of the current study is the development of a 'binding free energy fingerprint' specific to (5HT)-2A modulators, offering a novel metric for evaluating drug efficacy against this target. Our study demonstrates the prospective of employing a successful workflow combining AI with structural biology, offering a powerful tool for advancing psychoactive drug discovery. [Display omitted] • Developed machine learning models to classify bioactivity mechanisms for the 5HT-2A receptor. • Used datasets from BindingDB and ChEMBL, achieving 87 % accuracy with XGBoost and neural networks. • Combined AI models with molecular dynamics and MM-PBSA analysis for deeper insight into receptor-ligand interactions. • Introduced a 'binding free energy fingerprint' for evaluating modulators, aiding in 5HT-2A drug discovery. [ABSTRACT FROM AUTHOR]

Multiple myeloma is recognized as the second most common hematological cancer. MafA transcriptional repressor is an established mediator of myelomagenesis. While there are multitude of drugs available for targeting various effectors in multiple myeloma, current literature lacks a candidate RNA based MafA modulator. Thus, using the structure of MafA homodimer-consensus target DNA, a computational effort was implemented to design a novel RNA based chemical modulator against MafA. First, available MafA-consensus DNA structure was employed to generate an RNA library. This library was further subjected to global docking to select the most plausible RNA candidates, preferring to bind DNA binding region of MafA. Following global docking, MD-ready complexes that were prepared via local docking program, were subjected to 500 ns of MD simulations. First, each of these MD simulations were analyzed for relative binding free energy through MM-PBSA method, which pointed towards a strong RNA based MafA binder, RNA1. Second, through a detailed MD analysis, RNA1 was shown to prefer binding to a single monomer of the dimeric DNA binding domain of MafA using higher number of hydrophobic interactions compared with positive control MafA-DNA complex. At the final phase, a principal component analyses was conducted, which led us to identify the actual interaction region of RNA1 and MafA monomer. Overall, to our knowledge, this is the first computational study that presents an RNA molecule capable of potentially targeting MafA protein. Furthermore, limitations of our study together with possible future implications of RNA1 in multiple myeloma were also discussed. [Display omitted] • MafA is one of the factors that mediate multiple myeloma. • MafA lacks a RNA based modulator candidate. • RNA1 was selected from MD simulations followed by estimation of binding free energy. • RNA1 was capable of interacting with MafA through hydrophobic interactions. • PCA analyses led us to reveal actual binding site of RNA1 on MafA. [ABSTRACT FROM AUTHOR]

In this study, single crystal (sc) and nanocrystalline (nc) 3C-SiC samples were subjected to 30 keV He ion irradiation across various doses while maintaining a temperature of 800 °C. Employing techniques including Raman spectroscopy, transmission electron microscopy (TEM), and nanoindentation, the alterations in microstructure and hardness resulting from He irradiation with various fluences were examined. In sc-SiC, irradiation prompted the formation of He platelets, resulting in a hardness increase of 7 GPa. In contrast, nc-SiC, characterized by a higher stacking fault density, exhibited the formation of bubbles, primarily at grain boundaries (GBs), with fewer occurrences within the grain interior, leading to a hardness increase of 1 GPa. Notably, in both sc- and nc-SiC, hardness reached saturation and subsequently stabilized or declined with increasing He fluence. Through molecular dynamics (MD) cascade simulations, we discerned that various planar defects do not uniformly contribute to enhancing radiation resistance. For example, intrinsic stacking faults (ISF) and twins in SiC played a substantial role in altering defect density and configurations, thereby facilitating point defect annihilation. Conversely, extrinsic stacking faults (ESF) and Σ3 GBs had a limited impact on defect production during a cascade. Furthermore, calculations of cluster diffusivity revealed an accelerated movement of He-vacancy towards GBs compared to bulk material and other planar defects. Moreover, the scarcity of point defects and constrained mobility of He atoms towards stacking faults in nc-SiC elucidated the marked tendency of He to form platelets in sc-SiC. Additionally, our findings established a correlation between the calculated indentation hardness and the geometry of He defects, consistent with experimental results from nanoindentation. These results significantly contribute to ongoing efforts to design SiC materials with heightened radiation tolerance. [Display omitted] [ABSTRACT FROM AUTHOR]

Alkaline phosphatases (APs, EC 3.1.3.1) belong to a superfamily of biological macromolecules that dephosphorylate many phosphometabolites and phosphoproteins and their overexpression is intricated in the spread of cancer to liver and bones, neuronal disorders including Alzheimer's disease (AD), inflammation and others. It was hypothesized that cyclooxygenase-2 (COX-2) selective inhibitors may possess anti-APs potential and may be involved in anticancer proceedings. Three COX-2 inhibitors including nimesulide, piroxicam and lornoxicam were evaluated for the inhibition of APs using in silico and in vitro methods. Molecular docking studies against tissue nonspecific alkaline phosphatase (TNAP) offered the best binding affinities for nimesulide (−11.14 kcal/mol) supported with conventional hydrogen bonding and hydrophobic interactions. MD simulations against TNAP for 200 ns and principal component analysis (PCA) reiterated the stability of ligand-receptor complexes. Molecular expression analysis of TNAP enzyme in the breast cancer cell line MCF-7 exhibited 0.24-fold downregulation with 5 μM nimesulide as compared with 0.26-fold standard 10 μM levamisole. In vitro assays against human placental AP (hPAP) displayed potent inhibitions of these drugs with IC 50 values of 0.52 ± 0.02 μM to 3.46 ± 0.13 μM and similar results were obtained for bovine intestinal AP (bIAP). The data when generalized collectively emphasizes that the inhibition of APs by COX-2 inhibitors provides another target to work on the development of anticancer drugs. [Display omitted] [ABSTRACT FROM AUTHOR]

Fungal secondary metabolites have a long history of contributing to pharmaceuticals, notably in the development of antibiotics and immunosuppressants. Harnessing their potent bioactivities, these compounds are now being explored for cancer therapy, by targeting and disrupting the genes that induce cancer progression. The current study explores the anticancer potential of gliotoxin, a fungal secondary metabolite, which encompasses a multi-faceted approach integrating computational predictions, molecular dynamics simulations, and comprehensive experimental validations. In-silico studies have identified potential gliotoxin targets, including MAPK1, NFKB1, HIF1A, TDP1, TRIM24, and CTSD which are involved in critical pathways in cancer such as the NF-κB signaling pathway, MAPK/ERK signaling pathway, hypoxia signaling pathway, Wnt/β-catenin pathway, and other essential cellular processes. The gene expression analysis results indicated all the identified targets are overexpressed in various breast cancer subtypes. Subsequent molecular docking and dynamics simulations have revealed stable binding of gliotoxin with TDP1 and HIF1A. Cell viability assays exhibited a dose-dependent decreasing pattern with its remarkable IC 50 values of 0.32, 0.14, and 0.53 μM for MDA-MB-231, MDA-MB-468, and MCF-7 cells, respectively. Likewise, in 3D tumor spheroids, gliotoxin exhibited a notable decrease in viability indicating its effectiveness against solid tumors. Furthermore, gene expression studies using Real-time PCR revealed a reduction of expression of cancer-inducing genes, MAPK1, HIF1A, TDP1, and TRIM24 upon gliotoxin treatment. These findings collectively underscore the promising anticancer potential of gliotoxin through multi-targeting cancer-promoting genes, positioning it as a promising therapeutic option for breast cancer. [Display omitted] • The fungal secondary metabolite, Gliotoxin has emerged as a potential candidate with promising anticancer properties. • From the in-silico studies, MAPK1, NFKB1, HIF1A, TDP1, TRIM24, and CTSD were identified as the molecular targets of gliotoxin. • The results of molecular dynamics (MD) simulation analysis indicate that gliotoxin exhibits stable binding with TDP1 and HIF1A. • Gliotoxin has the ability to inhibit cancer-inducing genes in various breast cancer subtypes. • This study provides a pre-clinical rationale for evaluating gliotoxin as a potential candidate for breast cancer treatment. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a chronic neurodegenerative disorder that is the primary cause of dementia. It is characterised by the gradual loss of brain cells, which results in memory loss and cognitive dysfunction. One of the hallmarks of AD is an abnormally upregulated glutaminyl-peptide cyclotransferase (QPCT or QC) enzyme. Not only AD, but QC has also been implicated with pathological conditions like Huntington's disease (HD), melanomas, carcinomas, atherosclerosis, and septic arthritis. Therefore, the inhibition of QC emerged as a potential strategy for preventing multiple pathological conditions. Considering this, we screened a library of 153,536 imidazole-based compounds against a doubly mutant (Y115E-Y117E) QC target. Molecular docking based virtual screening and absorption, distribution, metabolism, excretion/toxicity (ADME/T) predictions identified five compounds, namely 118981836 , 136459842 , 139388116 , 139388226 , and 139958725. Furthermore, molecular dynamics (MD) simulations of 500 ns were conducted to investigate the behaviour of the identified compounds with the target receptor. The results were compared to the co-ligand by analysing RMSD, RMSF, and SASA parameters. To our knowledge, this is the first computational study that employed a protein with double mutation to identify new imidazole-based QC-inhibitors. [Display omitted] • In-silico studies on imidazole-based anti-ADs agents. • Five promising compounds were identified. • MD simulation studies to investigate the interactions at supramolecular level. [ABSTRACT FROM AUTHOR]

Cell membranes are responsible for a range of biological processes that require interactions between lipids and proteins. While the effects of lipids on proteins are becoming better understood, our knowledge of how protein conformational changes influence membrane dynamics remains rudimentary. Here, we performed experiments and computer simulations to study the dynamic response of a lipid membrane to changes in the conformational state of pH-low insertion peptide (pHLIP), which transitions from a surface-associated (SA) state at neutral or basic pH to a transmembrane (TM) α-helix under acidic conditions. Our results show that TM-pHLIP significantly slows down membrane thickness fluctuations due to an increase in effective membrane viscosity. Our findings suggest a possible membrane regulatory mechanism, where the TM helix affects lipid chain conformations, and subsequently alters membrane fluctuations and viscosity. [Display omitted] • Neutron spin echo spectroscopy reveals that transmembrane insertion of pHLIP reduces the rate of membrane thickness fluctuations. • Transmembrane pHLIP also increases membrane viscosity. • MD simulations reveal kinking of lipid chains around the helix, providing a potential mechanism for increased viscosity. • The effects are conformation-dependent, with no changes observed when pHLIP binds to the membrane surface at neutral to basic pH. [ABSTRACT FROM AUTHOR]

• In-silico screening of FDA drugs against Glyoxalase I. • Two-step molecular docking and molecular dynamics simulations. • Trilaciclib and Olmesartan were identified as potent inhibitors of Glyoxalase I. • Insights into inhibitor-enzyme interactions. • Trilaciclib and Olmesartan are also potent inhibitors of Glyoxalase II. This study employs structure-based in silico methodologies, including molecular docking and molecular dynamics (MD) simulations, to screen approximately 2500 FDA-approved drugs against the glyoxalase I enzyme. A two-step molecular docking approach was implemented, initially utilizing iGemdock software to screen the drugs, from which the top 20 compounds were selected for further analysis. Subsequent molecular docking in Autodock Vina, comparing scores with that of S -p-bromobenzyl-glutathione, a known enzyme inhibitor, identified 6 ligands for MD simulations. Results from the MD simulations highlight Trilaciclib and Olmesartan as potential glyoxalase I inhibitors. Furthermore, molecular docking indicated that these two drugs also exhibit potency as inhibitors of glyoxalase II. This suggests potential applications of Trilaciclib and Olmesartan as drugs for diseases modulated by the inhibition of the glyoxalase system. [ABSTRACT FROM AUTHOR]

• Systematical investigation of droplet impingement upon cylindrical surface at the nanoscale. • Reveal mechanisms underlying reduction of the contact time. • Reigmes of the contact time variation is obtained under various conditions. • Understanding of the effect of larteral wetting on the contact time variation. Engineering surfaces that can accelerate droplet detachment are of great importance to a wide range of practical applications, including dropwise condensation, anti-icing, and self-cleaning. Considering the pragmatic effect of reducing contact time (τ c), the cylindrical surface is one of the most popular passive approaches for achieving this purpose. Owing to the absence of a suitable way for the experimental observation, we use molecular dynamics (MD) simulations to obtain an in-depth understanding of droplet impingement on the curved surface at the molecular level together with the contact time variation. Accordingly, the regimes of τ c upon curved surfaces are well recognized by summarizing the τ c variation, which are stable reducing τ c regime and hybrid τ c regime. We propose a law of τ c ∝ α -0.226 to predict the τ c variation in the stable reducing τ c regime. And for the hybrid τ c regime, the τ c variation is specifically defined as three parts, including the delayed τ c , limited τ c , and transitional τ c regions. Moreover, we investigate the effect of the dimensionless length of curved surfaces on the τ c variation in detail. This work paves the way to design a more effective curved surface to promote the nanodroplet rebound. [ABSTRACT FROM AUTHOR]

[Display omitted] • Multi- and unilamellar liposomes (MLVs and LUVs) were prepared from POPE lipids. • Optical and molecular properties differ for MLVs- and LUVs derived aggregates. • Glycerol backbone of POPE lipids in H II phase is hydrated better that in L α phase. • Hydrogen bonds intertwined by phosphate and amino groups depend on POPE phase. Membrane fusion is closely related to plasma membrane domains rich in cone-shaped phosphatidylethanolamine (PE) lipids that can reverse membrane curvature under certain conditions. The phase transition of PE-based lipid membranes from the lamellar fluid phase (L α) to the inverse hexagonal phase (H II) is commonly taken as a general model in reconstructing the membrane fusion pathway, and whose structural features have been mostly described so far using structural and microscopic techniques. The aim of this paper is to decipher the optical and molecular features of L β → L α and especially of L α → H II transition of 1-palmitoyl-2-oleoyl- sn -glycero-3-phosphoethanolamine (POPE) lipids at pH = 7.0 when they are initially prepared in the form of both multi- and unilamellar liposomes (MLVs and LUVs). The distinction between optical properties of MLS- and LUVs-derived H II phase, provided from turbidity-sensitive temperature-dependent UV–Vis spectra, was attributed to different formation mechanisms of H II phase. Most importantly, from FTIR spectroscopic data of POPE lipids in L β (15 °C), L α (50 °C) and H II (85 °C) phases we identified the changes in molecular features of POPE lipids during phase transitions. Among the latter, by far the most significant is different hydration pattern of POPE lipids in MLVs- and LUVs-derived H II phase which extends from the polar-apolar interface all the way to the terminal amino group of the POPE lipid, along with the changes in the conformation of glycerol backbone as evidenced by the signature of α-methylene groups. Molecular dynamics simulations confirmed higher water penetration in H II phase and provided insight into hydrogen bonding patterns. [ABSTRACT FROM AUTHOR]

• Superimposition docking studies revealing similarity in binding modes of Patuletin and Remdesivir against the RdRp. • MD simulations (200 ns) confirming stability and optimal changes. • MM-GBSA and 3D binding interactions analysis showing favorable and stable binding. • PCAT providing insights into dynamic behavior. • In vitro assays demonstrating exceptional potency with superior efficacy and safety margin of Patuletin over Remdesivir against the RdRp and SARS-CoV-2. In the pursuit of identifying effective inhibitors against SARS-CoV-2, we conducted a detailed investigation into the binding interactions and inhibitory potential of Patuletin targeting the RNA-Dependent RNA Polymerase (RdRp), comparing it with the well-known anti-RdRp agent, Remdesivir. Superimposition molecular docking studies uncovered a high degree of similarity in binding modes between Patuletin and Remdesivir within the active site of the RdRp. MD simulations (RMSD, RMSF, RG, SASA, hydrogen bonding) over a 200 ns trajectory provided valuable insights into the binding and interactions of Patuletin and RdRp comparing Remdesivir. These simulations validated the correct binding and optimum changes in both energetic and dynamic aspects, confirming the stability of the Patuletin-RdRp complex comparing the Remdesivir-RdRp complex. Further, the MM-GBSA technique revealed favorable binding energies, with Patuletin displaying a significantly lower value (-4.24 kcal/mol) compared to Remdesivir (-2.15 kcal/mol), affirming the robustness of Patuletin-RdRp binding. The MM-GBSA analysis additionally examined the binding energetic components, revealing a high degree of similarity between Patuletin and Remdesivir. 3D binding interactions were investigated through ProLIF and PLIP studies reinforcing the stable binding observed in the simulations. Principal component analysis of trajectories (PCAT) studies were employed to discern coordinated motions within the evaluated systems, providing additional perspectives on the dynamic behavior of the Patuletin-RdRp complex. In vitro assays demonstrated Patuletin's exceptional inhibitory potency against the RdRp, with an IC 50 of 248 nM, far surpassing Remdesivir, which exhibited an IC 50 of 20 µM. Interestingly, the in vitro IC 50 against SARS-CoV-2 values further supported the superior efficacy of Patuletin (0.476 µg/ml) over Remdesivir (10.86 µg/ml). Furthermore, the viral selectivity index (SI) values highlighted the remarkable safety margin of Patuletin (SI: 790.76) compared to Remdesivir (SI: 5.87), underscoring the potential of Patuletin as a safer and more potent therapeutic agent against SARS-CoV-2. In conclusion, our comprehensive analysis presents Patuletin as a promising candidate for further exploration as a potent inhibitor of SARS-CoV-2 RdRp, offering valuable insights for the development of effective anti-COVID-19 therapies. [ABSTRACT FROM AUTHOR]

[Display omitted] • DFT study showed improvement on hydrogen storage properties of ZTC upon ZnCl 2 and KOH activation. • Simulation showed an increase of SSA and ASA in the ZTAC after the activation process. • Maximum hydrogen storage capacity was 5.2 and 5.95 wt% activated with ZnCl 2 and KOH. • Hydrogen storage capacity of ZTAC met the DOE target by 2025. In this study, Density Functional Theory (DFT) simulation method was applied to show that hydrogen-storage properties of Zeolite Templated Carbon (ZTC) can be enhanced via chemical activation. Study results calculated via simulation and the Monte Carlo integration technique showed that in comparison to unactivated ZTC, the theoretical specific surface area (SSA) for Zeolite Templated Activated Carbon (ZTAC) increased by 4.79 and 2.13 %, when activated with either Zinc dichloride (ZnCl 2) or Potassium Hydroxide (KOH), respectively. In addition, calculation of accessible surface area (ASA) resulted in 7809.40 m2/g and 7611.74 m2/g, correspondingly. Simulations of H 2 adsorption revealed that H 2 molecules were adsorbed primarily on the concave region of the ZTAC. Also, it was found the that the largest amount of H 2 adsorbed molecules on ZTAC activated with either ZnCl 2 or KOH were 13 and 15, and the average binding energies were 0.184 eV and 0.202 eV, respectively. In this regard, the maximum hydrogen storage capacity obtained in this study was 5.2 wt% (ZTAC-13H 2) and 5.95 wt% (ZTAC-15H 2) with a volumetric density of 0.065 kg H 2 /L and 0.074 kg H 2 /L for the ZTAC activated with either ZnCl 2 or KOH. These results are in accordance with the U.S. Department of Energy (DOE) ultimate target by the 2025 year. In addition, thermal stability and desorption temperatures of ZTAC structures were determined via molecular dynamics simulations and through the van't Hoff equation, showing that hydrogen molecules were easy to desorb at room temperature (T =300 K). These results pose these systems suitable for automotive onboard applications, leading to future research on synthesis techniques of ZTAC materials which certainly require more experimental investigation. [ABSTRACT FROM AUTHOR]

Gonadotropin-releasing hormone (GnRH) is the main regulator of the reproductive system, acting on gonadotropic cells by binding to the GnRH1 receptor (GnRH1R). Traditionally, therapies targeting this receptor have relied on peptide modulators, which required subcutaneous or intramuscular injections. Due to the limitations of the parenteral administrations, there is a growing interest in developing oral small molecule modulators of GnRH1R as more convenient therapeutic alternatives. In this study, we examined the potential of chemically modifying elagolix, the first approved non-peptide, orally active GnRH1R antagonist, to increase its atropisomeric properties by introducing new moieties. We designed and synthesized the thio-uracil (1) and cytosine (2) derivatives of elagolix, both demonstrating GnRH1R antagonistic activities, with EC 50 values of 39 and 110 nM, respectively. The atropisomers of 1 and 2 were efficiently separated using silica gel chromatography, and extensive NMR investigation, supported by Density Functional Theory (DFT) calculations, allowed us to define their conformations and rotational barriers. Docking and Molecular Dynamics (MD) studies revealed that 1 and 2 bind to GnRH1R with ΔG values comparable to elagolix, but through distinct binding modes. These results highlight the potential of non-peptide modulators to effectively modulate GnRH1R activity and pave the way for developing novel modulators. [Display omitted] • New thio-uracil (1) and cytosine (2) derivatives based on elagolix were designed, synthesized and their structures confirmed. • Atropisomers of 1 and 2 showed higher stability than atropisomers of elagolix. • Derivatives 1 and 2 of elagolix possess nanomolar GnRH1R antagonistic activities in vitro and cellular assays. • MD studies revealed that 1 and 2 bind to GnRH1R through distinct binding modes. [ABSTRACT FROM AUTHOR]

This study aims to assess the effectiveness of mCSM-AB2, a graph-based signature machine learning method, for affinity engineering of the humanized single-chain Fv anti-CD147 (HuScFvM6-1B9). In parallel, molecular dynamics (MD) simulations were used to gain valuable insights into the dynamics and affinity of the HuScFvM6-1B9-CD147 complex. The result analysis involved integrating free energy changes calculated from the mCSM-AB2 with binding free energy predictions from MD simulations. The simulated structures of the modified HuScFvM6-1B9-CD147 domain 1 complex from MD simulations were used to highlight critical residues participating in the binding surface. Interestingly, alterations in the pattern of amino acids of HuScFvM6-1B9 at the complementarity determining regions interacting with the 31EDLGS35 epitope were observed, particularly in mutants that lost binding activity. The predicted mutants of HuScFvM6-1B9 were subsequently engineered and expressed in E. coli for subsequent binding property validation. Compared to WT HuScFvM6-1B9, the mutant HuScFvM6-1B9L1:N32Y exhibited a 1.66-fold increase in binding affinity, with a K D of 1.75 × 10−8 M. While mCSM-AB2 demonstrates insignificant improvement in predicting binding affinity enhancements, it excels at predicting negative effects, aligning well with experimental validation. In addition to binding free energies, total entropy was considered to explain the discrepancy between mCSM-AB2 predictions and experimental results. This study provides guidelines and identifies the limitations of mCSM-AB2 and MD simulations in antibody engineering. [Display omitted] • mCSM-AB2 excels at predicting affinity loss but struggles with affinity gains. • Combining mCSM-AB2 with MD simulations enhances predictive power. • Entropy explains the discrepancy of MD simulation and mCSM-AB2. • Machine learning should consider complex stability and structure flexibility. [ABSTRACT FROM AUTHOR]

[Display omitted] Pregnane X receptor (PXR) is a heterologous biosensor that is involved in the metabolic pathway of environmental pollutants, regulating the transcription of genes involved in biotransformation. There are significant differences in the selectivity and specificity of organic pollutants (OPs) toward polar bear PXR (pbPXR) and human PXR (hPXR), but the detailed dynamical characteristics of their interactions are unclear. Homology Modeling, molecular docking, molecular dynamics simulation, and free energy calculation were used to analyze the recognition of pbPXR and hPXR by three OPs: BPA, chlordane and toxaphene. Comparing interaction patterns along with binding free energy of pbPXR and hPXR with these three OPs revealed that although pbPXR and hPXR interact similar with these three OPs, these OPs have different effects on the internal dynamics of pbPXR and hPXR. This results in significant alterations in the interaction of key residues near Leu209, Met243, Phe288, Met323, and His407 with OPs, thereby influencing their binding energy. Non-polar interactions, especially van der Waals interactions, were found to be the dominating factors in interacting of these OPs with PXRs. The region surrounding these key residues facilitates hydrophobic contacts with PXR, which are crucial for the selective activation of PXRs in different species by these three OPs. These findings are of significant guidance in understanding the impacts of environmental endocrine disruptors on different organisms. [ABSTRACT FROM AUTHOR]

• Laser focus depth and pressure determine the graphitization or amorphization of SiC. • Correlation between scanning speed and focal overlap rate was established by defining an intensity factor. • Correlation between laser fluence and damage width was studied by molecular dynamics modeling. • Regulation of thermal damage was achieved by using a damage regulation strategy. Picosecond laser modification dicing (PLMD), compared with blade dicing, is more suitable for high-efficiency and low-damage processing of high hardness and brittleness SiC materials. However, the potential thermal damage restricts the further promotion of PLMD technology. To solve this problem, in this paper, the thermal damage behavior and mechanism of PLMD are studied by means of experiment and molecular dynamics (MD) simulations. In sidewall, the thermal damage manifests as thermal decomposition and amorphization. The thermal decomposition, which is essentially the graphitization caused by the gasification of Si and enrichment of C, occurs in the atmospheric pressure modified layers. The amorphization, caused by 470.0 GPa high pressure and 1.58 × 1013K/s cooling rate, occurs in the high pressure modified layers. Other forms of thermal damage, including cracking, chipping, and oxidation, are caused by heat accumulation in kerf region. The focal overlap rate is refined through an intensity correction factor, then transformed into the effective pulse number, serving as input for the model. This contributes to model with an average accuracy of 81 %. By adopting a thermal damage regulation strategy, PLMD of SiC wafers without thermal damage is realized. [ABSTRACT FROM AUTHOR]

Interleukin-8 (IL-8) is a chemokine, a type of signaling molecule that has a role in immunological responses and inflammation. In recent years, IL-8 is additionally related to cancer growth and recurrence. Breast cancer growth, progression, and metastatic development are all linked to IL-8. Breast cancer cells are known to develop faster when IL-8 stimulates their proliferation and survival. It can also cause angiogenesis, or the creation of new blood vessels, which is necessary for tumor nutrition and growth. IL-8 and curcumin have been subjects of interest in drug design, particularly in the context of inflammation-related disorders and cancer. This study aims to give an overview of the role of IL-8. Inhibitor-based treatment approaches were being used to target IL-8 with curcumin. Molecular docking method was employed to find a potential interaction to supress competitive inhibition of IL-8 with curcumin. PASS analysis and ADMET characteristics were also being carried out. In the end, IL-8 complexed with curcumin is chosen for MD simulations. Overall, our results showed that during the simulation, the complex stayed comparatively stable. It is also possible to investigate curcumin further as a possible treatment option. The combined results imply that IL-8 and their genetic alterations can be studied in precision cancer therapeutic treatments, utilizing target-driven therapy and early diagnosis. [ABSTRACT FROM AUTHOR]

[Display omitted] • TiO 2 quantum dots (QDs) modified asphalt has been proposed as an innovative cool pavement technology. • Electronic and optical characteristics of TiO 2 QDs are investigated based on quantum mechanics calculations. • Modification mechanism and properties of TiO 2 QDs modified asphalt are evaluated based on molecular dynamics simulations. • Impacts of quantum sizes and concentrations on properties of TiO 2 QDs modified asphalt are analyzed. With exceptional solar reflectivity and fluorescent characteristics, TiO 2 quantum dots (QDs) modified asphalt has been proposed as an innovative cool pavement technology. However, interaction mechanism and thermodynamic properties of TiO 2 QDs modified asphalt at microscale have not been well understood. In this study, electronic and optical properties of TiO 2 QDs with varied sizes were investigated based on quantum mechanics (QM) calculations. Moreover, molecular dynamics (MD) simulations were implemented to evaluate mechanical moduli and intermolecular dynamics of TiO 2 QDs modified asphalt with different quantum sizes and concentrations. The results from QM calculations unveil that as size of TiO 2 QDs rises from 6 Å to 12 Å, energy gap and binding energy of TiO 2 QDs decreases by 0.928 eV and 526.38 eV, respectively while density of state (DOS) and absorption coefficient of TiO 2 QDs increases. Besides, the results from MD simulations reveal that quantum size imposes significant impact on mechanical moduli of modified asphalt while concentration of TiO 2 QDs brings notable influence on interaction between quantum dots and asphalt. Specifically, as concentration of QDs rises from 10 % to 30 %, cohesive energy density (CED) and solubility parameter (SP) of modified asphalt is improved by up to 457 % and 136 %, respectively. With increasing quantum size, bulk modulus, shear modulus, and Young's modulus of modified asphalt is enhanced by up to 372 %, 206 % and 24 %, respectively. The outcomes of this study provide insights into formula and application of advanced asphalt pavement with TiO 2 QDs. [ABSTRACT FROM AUTHOR]

• The interfacial properties and reactivities of S N 2 reaction induced by interfacial polar microenvironments of COFs were investigated. • The decreased nanopore size of COFs can enlarge reaction rates and reduce activation energy barriers. • The hydroxyl-modified COF can further cause larger reaction rates and lower activation energy barriers. Given the poor understanding about the effects of confined polar microenvironment on interfacial behaviors of Menshutkin S N 2 reaction, herein, the interfacial properties and reactivities between 1-methylimidazole and methyl thiocyanate reaction induced by interfacial polar microenvironments of covalent organic frameworks (COFs) with varying pore size and functional groups were investigated using in situ Fourier transform infrared spectroscopy, molecular dynamics simulations, and metadynamics calculations. The decreased nanopore size of COFs from 3.2 to 1.2 nm can enlarge reaction rates (k) and reduce activation energy barriers (Δ E *). The hydroxyl-modified COF (2.8 nm) can further cause larger k and lower Δ E * by 6.1 and 0.8 kJ/mol compared to the bulk and smaller pore-size COF (1.2 nm) system, respectively, mainly originating from induced higher aggregation, preferred orientation, and the stabilization of charge separation of transition state. This work provides a systematic understanding for the confined interfacial properties toward accelerating the Menshutkin reaction. [ABSTRACT FROM AUTHOR]

Solvent-resistant nanofiltration membranes, capable of breaking "trade-off" between permeability and selectivity while resisting physical aging, hold crucial utility in developing advanced membrane materials and reducing energy consumption associated with solvent recovery. Herein, the development of scalable, mixed matrix membranes (MMMs) was presented based on polysulfone (PSf) substrate with ultra-high permeability and aging resistance. The upper selective layer was composed of poly-trimethylsilylpropyne (PTMSP) and two types of nano-fillers, namely poly-dichloroxylene (p -DCX) and sodium dodecylbenzene sulfonate-molybdenum sulfide (SDBS-MoS 2). Under the influence of the additives, the redistribution of the free volume of the polymer as well as the internal spaces within additives creates additional pathways for solvent diffusion, thus increasing solvent permeance. Additionally, the combined effect of the two additives is likely to inhibit filler agglomeration and improve the overall effectiveness of the additives. Compared to pure PTMSP membranes, the p -DCX/SDBS-MoS 2 PTMSP MMMs exhibited enhanced methanol permeance (10.58 vs. 3.14 L m−2 h−1 bar−1) and RB rejection (99.23 vs. 96.13 %), which greatly exceeded that of current OSN MMMs. As anticipated, aging of the prepared membranes decelerated with the addition of the additives, and the methanol permeation loss rate decreased from 50.32 % to 13.23 % after 300 h. Molecular dynamics simulations explored by structural analysis revealed the mechanism for the significant improvement in methanol permeance and aging resistance. The membranes obtained were found to be highly industrially applicable, thereby offering the potential to reduce operation costs in energy-intensive separation processes. [Display omitted] • High performance OSN MMMs were prepared by blending p -DCX and SDBS-MoS 2 into PTMSP polymer. • The synergistic effect of the two additives imparted outstanding permeance and selectivity to the membrane. • The anti-aging capability of the membrane could be improved by incorporating p -DCX and SDBS-MoS 2. • MD simulations revealed the mechanism of enhanced membrane performance by nano-additives. [ABSTRACT FROM AUTHOR]

SIRT6 is of interest for its promising effect in the treatment of aging-related diseases. Studies have shown quercetin (QUE) and its derivatives have varying degrees of effect on the catalytic effect of SIRT6. In the research, the effect of QUE on the protein-substrate interaction in the SIRT6-mediated mono-ADP ribosylation system was investigated by conventional molecular dynamics (MD) simulations combined with MM/PBSA binding free energy calculations. The results show that QUE can bind stably to SIRT6 with the binding energy of −22.8 kcal/mol and further affect the atomic interaction between SIRT6 and NAD+ (or H3K9), resulting in an increased affinity between SIRT6-NAD+ and decreased SIRT6-H3K9 binding capacity. At the same time, the binding of QUE can also alter some structural characteristics of the protein, with large shifts occurring in the residue regions involving the N-terminal (residues 1–27), Rossmann fold regions (residues 55–92), and ZBD (residues 164–179). Thus, QUE shows great potential as a scaffold for the design of novel potent SIRT6 modulators. The binding of Quercetin with SIRT6 affects the protein-ligand interaction in the SIRT6-mediated mono-ADP ribosylation system. [Display omitted] • Quercetin and its derivatives affect protein-substrate interactions in the SIRT6-mediated mono-ADP ribosylation reaction. • Quercetin has a binding energy of −22.8 kcal/mol and may attach to SIRT6 steadily. • Quercetin results in an increased affinity between SIRT6-NAD+ and decreased SIRT6-H3K9 binding capacity. • The binding of quercetin results in alterations to the structural characteristics of the SIRT6 protein. [ABSTRACT FROM AUTHOR]

• Chain lengths' effects of epoxy resins on both the crosslinking process and thermomechanical properties were investigated by molecular dynamics simulations. • The main reason why it is difficult to achieve the desired conversion rate in the experiment was revealed. • The molecular mechanism of chain length on thermal conductivity and other various thermomechanical properties is unified by our systematic study. Epoxy resin is commonly used as the matrix in carbon fiber-reinforced polymer (CFRP), fabricated through the curing reaction of the base resin and curing agent, whose properties have a deep relationship with the crosslinking degree of the polymer. However, under certain circumstances, the desired conversion rate cannot be achieved in the experiments. To shed light on this phenomenon and the underlying mechanisms, the curing process of diglycidyl ether of bisphenol A (DGEBA) with different chain lengths and 4,4′-diamino diphenyl sulfone (4,4′-DDS) was simulated as per our previously developed crosslinking algorithm. The longer chain length postpones but does not change the reaction progress (like the gel point), leading to a lower conversion rate, and ultimately a decrease in the diffusion coefficient. In addition, the influence on the glass transition temperature is the result of the competing effects of the conversion rate and monomer diffusivity. Moreover, the negligible effect on thermal conductivity is closely linked with a slight change in the monomeric degree index (MDI), reflecting the whole internal intrinsic structure. Furthermore, the effect on Young's modulus and yield stress has a deep relationship with the ring degree index (RDI), i.e., higher RDI demands more non-bonded energy for the collective movement of monomer chains. Our systematic investigation unifies the mechanism of the impact of chain length on various thermomechanical properties, which is instructive for the improved performance of epoxy resins. [ABSTRACT FROM AUTHOR]

• With the temperature decreasing from 25 to −180 °C, the uniform elongation and post-necking elongation of the alpha titanium sheets were increased by 92 % and 20 %, respectively. • The uniform plastic deformation was mainly accomplished by prismatic slip both at room and cryogenic temperatures, and the excellent cryogenic ductility is mainly attributed to the more uniform distribution of GNDs. • Cryogenic temperatures caused a stronger barrier effect of GBs on dislocation transmission compared with that at room temperature, contributing to the more uniform distribution of GNDs and lower densities of GND pile-ups. • Considering the great ability of GBs to resist void nucleation, the large strains were required to increase the densities of GND pile-ups to reach the stress threshold of void nucleation, resulting in the excellent cryogenic ductility. Alpha titanium (α-Ti) is a promising material for making high-performance components for applications in aerospace, marine, energy and healthcare fields. The excellent strength-ductility synergy has been observed for α-Ti at cryogenic temperature. Twinning is generally considered a key mechanism of outstanding cryogenic ductility. The dislocation-grain boundaries (GBs) interaction and void nucleation usually play crucial roles in the plastic deformation of polycrystalline materials, but their effects on the cryogenic ductility of α-Ti are rarely considered. To eliminate this confusion and gain an in-depth insight into the mechanism of the cryogenic strength-ductility synergy of α-Ti, in this work, a series of characterization experiments and molecular dynamics (MD) simulations were designed and carried out. 1) From uniaxial tension tests of the coarse-grained α-Ti sheets at the temperature from 25 to -180 °C, the uniform elongation and post-necking elongation were increased by 92 % and 20 %, respectively. The material maintained a larger strain hardening rate within a greater range of strain at cryogenic temperature compared with room temperature. 2) Via microstructure and fractography observations and the analysis of slip and geometrically necessary dislocation (GND) activities, the uniform plastic deformation was mainly accomplished by prismatic slip, whether at room temperature or at cryogenic temperature. The significantly increased uniform elongation is mainly attributed to the more uniform distribution of GND pile-ups at cryogenic temperature. 3) The MD simulations revealed that cryogenic temperatures made the GBs present a stronger barrier effect on dislocation transmission compared with that at room temperature, contributing to the more uniform distribution of GNDs and lower densities of GND pile-ups. The GBs at cryogenic temperature show a greater ability to resist void nucleation due to the decreased accumulation rate of excess potential energy and increased energy required to void nucleation. The larger strains were thus required to increase the densities of GND pile-ups to induce large stress concentrations for driving void nucleation. This made the uniform elongation of α-Ti increase significantly at cryogenic temperature. This study revealed that the enhanced barrier effect of GBs on dislocation transmission and the improved ability of GBs to resist void nucleation are key mechanisms besides twinning governing the cryogenic strength-ductility synergy of α-Ti. The understanding developed in this work can be useful for the development of new high-performance materials and the precise forming of complex components with high quality. [ABSTRACT FROM AUTHOR]

VEGFR-2 has emerged as a prominent positive regulator of cancer progression. Discovery of new anticancer agents and apoptotic inducers targeting VEGFR-2. Design and synthesis of new thiazolidine-2,4-diones followed by extensive in vitro studies, including VEGFR-2 inhibition assay, MTT assay, apoptosis analysis, and cell migration assay. In silico investigations including docking, MD simulations, ADMET, toxicity, and DFT studies were performed. Compound 15 showed the strongest VEGFR-2 inhibitory activity with an IC 50 value of 0.066 μM. Additionally, most of the synthesized compounds showed anti-proliferative activity against HepG2 and MCF-7 cancer cell lines at the micromolar range with IC 50 values ranging from 0.04 to 4.71 μM, relative to sorafenib (IC 50 = 2.24 ± 0.06 and 3.17 ± 0.01 μM against HepG2 and MCF-7, respectively). Also, compound 15 showed selectivity indices of 1.36 and 2.08 against HepG2 and MCF-7, respectively. Furthermore, compound 15 showed a significant apoptotic effect and arrested the cell cycle of MCF-7 cells at the S phase. Moreover, compound 15 had a significant inhibitory effect on the ability of MCF-7 cells to heal from. Docking studies revealed that the synthesized thiazolidine-2,4-diones have a binding pattern approaching sorafenib. MD simulations indicated the stability of compound 15 in the active pocket of VEGFR-2 for 200 ns. ADMET and toxicity studies indicated an acceptable pharmacokinetic profile. DFT studies confirmed the ability of compound 15 to interact with VEGFR-2. Compound 15 has promising anticancer activity targeting VEGFR-2 with significant activity as an apoptosis inducer. • New VEGFR-2 inhibitors based on thiazolidine-2,4-diones have been designed and synthesized. • Anti-proliferative and VEGFR-2 inhibitory activity were tested. • Cell cycle and apoptosis analyses were assessed. • In silico docking, MD simulation, DFT, ADMET, and toxicity studies were performed. [ABSTRACT FROM AUTHOR]

Despite its importance for nanofluidic systems, achieving continuous water flow in long nanochannels remains a major challenge. Here, we propose a general principle to overcome this challenge by introducing a method that involves the building of a series of cascadable driving units, each unit carrying a net thermal gradient force, to maintain continuous water flow in an arbitrarily long nanochannel. Using molecular dynamics simulations and analytical modeling, we show that, within a single driving unit, the net thermal gradient force can be achieved through a multitude of strategies, including geometrical (e.g., a localized confinement), mechanical (e.g., a localized pinch), electrical (e.g., a point electric charge) and chemical (e.g., a point functionalization). The proposed method has fundamental significance for nanofluidic systems and potential applications in nanoscale mass transport and energy conversion devices. [Display omitted] [ABSTRACT FROM AUTHOR]

Magnesium (Mg) based alloys are promising candidates for many applications, but their untreated surfaces usually have low strength and hardness. In this study, a single point diamond turning (SPDT) technique was applied to refine the grain size and improve the mechanical properties of the surface layers of Mg-Li alloys. By refining grains in the topmost layer to the nanometer scale (∼ 60 nm), the surface hardness was found to be enhanced by approximately 60%. The atomic plastic deformation process during the SPDT was then studied by the real-time atomistic molecular dynamics (MD) simulations. A series of MD simulations with different combinations of parameters, including rake angle, cutting speed and cutting depth, were conducted to understand their influences on the microstructural evolution and associated plastic deformation mechanisms on the surface layer of the workpieces. The MD simulation results suggest that using increased rake angle, cutting speed and cutting depth can help to achieve better grain refinement. These simulation results, which provide atomic-level details of the deformation mechanism, can assist the parameter design for the SPDT techniques to achieve the high-performance heterogeneous nanostructured materials. [ABSTRACT FROM AUTHOR]

The widespread demand for clean energy stimulates great interest to hydrogen energy with high energy density and conversion efficiency. Separation technologies by membranes are increasingly applied for hydrogen separation because of its excellent performance and low consumption. In this work, density functional theory simulations is used to study hydrogen separation of Pd–Au–Ag membrane, and the performance of Pd–Au alloy is also compared and discussed. The results indicate that Pd–Au alloy shows superior selectivity to H 2 gas over CO, N 2 , CH 4 , CO 2 and H 2 S gases, which is in line with experimental results. In particular, the separation selectivity of Pd–Au–Ag to H 2 is significantly greater than those for Pd–Au alloy and several currently reported materials. Moreover, the permeability of H 2 in Pd–Au–Ag exceeds the limits for industrial production at deferent temperatures. Our calculations demonstrate that Pd–Au–Ag alloy present excellent performance as a promising membrane for hydrogen separation. [Display omitted] • For the first time, hydrogen selectivity and permeance of Pd–Au–Ag are studied. • The predicted H 2 separation performance of Pd–Au consists with experiments. • Selectivity of Pd–Au–Ag alloy to H 2 is much greater than that of Pd–Au alloy. • Permeance of H 2 exceed the industrial production limit at various temperatures. • Our method can be used to evaluate permeability and selectivity of alloy membrane. [ABSTRACT FROM AUTHOR]

We have investigated the hydrogen storage capabilities of scandium decorated holey graphyne, a recently synthesized carbon allotrope, by applying density functional theory and molecular dynamics simulations. We have observed that one unit cell of holey graphyne can adsorb 6 Sc atoms, and each Sc atom can adsorb up to 5H 2 molecules with an average binding energy and average desorption temperature of −0.36 eV/H 2 and 464 K, respectively. The gravimetric weight percentage of hydrogen is 9.80%, which is considerably higher than the Department of Energy, United-States requirements of 6.5%. We have found that a total amount of 1.9e charge transfers from the 3d and 4s orbitals of Sc atom to the C-2p orbitals of holey graphyne by performing the Bader charge analysis. Hydrogen molecules are bonded with the scandium atom by Kubas interactions. The ab-initio molecular dynamics simulations confirm the structural integrity of scandium decorated holey graphyne system at the high desorption temperatures. The presence of sufficient diffusion energy barriers for the Sc atom ensure the avoidance of metal-metal clustering in the system. [Display omitted] • Using DFT and AIMD, H 2 storage in Sc decorated holey graphyne is reported. • Single Sc adsorbs 5H 2 molecules leading 9.80 wt %. • Molecular dynamics simulations ensure solidity of structure. • Sufficient diffusion energy barrier prevents metal-metal clustering. • H 2 molecules are attached on Sc by Kubas interactions with average BE of −0.36 eV/H 2. [ABSTRACT FROM AUTHOR]

Tungsten is used as plasma-facing wall in ITER where is subjected to extreme operating conditions. In this work, we study the formation damage in [111] crystalline W by neutron bombardment in the temperature range of 300–900 K which is important for designing next generation of fusion reactors. Molecular Dynamics (MD) simulations are performed at a primary knock-on atoms (PKA) energy of 1 keV within the Gaussian Approximation Potential (GAP) framework. The analysis of the induced damage is done by the Fingerprinting and Visualization Analyzer of Defects (FaVAD) which is based on a rotation invariant mapping of the local atomic neighborhoods allowing to extract, to identify and to visualize the atomic defect formation dynamically during and after the collision cascades. The evaluation allows to classify several defect types and to quantify the defect evolution as function of time and initial sample temperature. We found that the production of Frenkel pair increases as a function of the temperature due to thermal activated mechanisms. [ABSTRACT FROM AUTHOR]

Human transferrin (Tf) is an iron-binding blood plasma glycoprotein that controls free iron in biological fluids. Tf is a liver-produced protein that binds iron very tightly but reversibly and is the most significant iron pool. Memantine is an orally administrative N -methyl- d -aspartate glutamate receptor antagonist used to slow the progression of moderate-to-severe Alzheimer's disease (AD) and dementia. Here, we have investigated the molecular interactions of Memantine with Tf using molecular docking, dynamics simulation and in vitro binding studies. Molecular docking study revealed many close interactions of Memantine towards Tf with an appreciable binding affinity. The docking results were further validated by molecular dynamics (MD) simulation studies, followed by essential dynamics and free energy landscapes analyses. Memantine shows a good binding affinity to the Tf with a binding constant (K) of 105 M-1. Isothermal titration calorimetry (ITC) also advocated the spontaneous binding of memantine to Tf. The study proposed that the Memantine in complex with Tf is stable in the simulated trajectory with minimal structural changes. The study suggested that the Tf-Memantine interactions can be further explored in AD therapy after critical exploration. • Homeostasis of metal ions in the brain is vital for normal physiological functions. • Transferrin is a key player in iron homeostasis and fourth richest plasma protein. • Memantine shows a good binding affinity to the Tf with a binding constant (K) of 105 M-1. • Isothermal titration calorimetry (ITC) also advocated spontaneous binding. • Tf-memantine complex is stable in simulated trajectory with minimal structural changes. [ABSTRACT FROM AUTHOR]

Self-assembled chemically modified graphene (CMG) aerogels with high compressive elasticity are important materials because of their unique properties and broad applications, but there is a lack of guiding principles for the design of elastic CMG aerogels. In this work, we provide new insights into the elasticity of chemical modified graphene aerogels. We demonstrate that the self-assembled CMG aerogels have intrinsic compressive elasticity, and report a reversible transition of CMG aerogels from elasticity to plasticity caused by water adsorption. Experimental data and molecular dynamics simulations show that water molecules on the surface of the ultrathin CMG cell walls in the aerogel form a hydrogen bond network, which hinders the shape recovery of the bent cell walls and plasticize the aerogel. A general method is then developed to enhance the elasticity of CMG aerogel by reducing its surface hydrophilicity with thermal treatment. The method efficiently imparts good elasticity to aerogels prepared by conventional hydrothermal methods. This work clarifies the important influence of water surface plasticization on the elasticity of CMG aerogels, and provides principles for the design of highly elastic aerogels based on low dimensional nanomaterials. [Display omitted] • The chemically converted graphene aerogels have intrinsic compressive elasticity. • Absorbed water reduces the elasticity of the aerogels by surface plasticization. • Removing oxygenated groups improves the elasticity of the aerogels in the air. [ABSTRACT FROM AUTHOR]

Peptide toxins are potent and often exquisitely selective probes of the structure and function of ion channels and receptors, and are therefore of significant interest to the pharmaceutical and biotech industries as both pharmacological tools and therapeutic leads. The three-dimensional structures of peptide toxins are essential as a basis for understanding their structure-activity relationships and their binding to target receptors, as well as in guiding the design of analogues with modified potency and/or selectivity for key targets. NMR spectroscopy has played a key role in elucidating the structures of peptide toxins and probing their structure-function relationships. In this article, we highlight the additional important contribution of NMR to characterising the dynamics of peptide toxins. We also compare the information available from NMR measurements with that afforded by molecular dynamics simulations. We describe several examples of the importance of dynamics measurements over a range of timescales for understanding the structure-function relationships of peptide toxins and their receptor engagement. Peptide toxins that inhibit the voltage-gated potassium channel K V 1.3 with pM affinities display different degrees of conformational flexibility, even though they contain multiple disulfide bonds, and this flexibility can affect the relative orientation of residues that have been shown to be critical for channel binding. Information on the dynamic properties of peptide toxins is important in the design of analogues or mimetics where receptor-bound structures are not available. [Display omitted] • Disulfide-rich peptide toxins can exhibit significant conformational flexibility. • While disulfide bonds confer overall structural stability, they can also be a source of conformational exchange. • Nuclear magnetic resonance spectroscopy is a valuable tool for probing dynamics over a broad range of timescales. • Dynamics can influence structure-function relationships of peptide toxins and their binding to receptors. • Dynamics should also be considered when designing analogues or mimetics of peptide toxins. [ABSTRACT FROM AUTHOR]

Hydrogen is one of the most prospective energy resources with zero polluted emission and high energy utilization, an improved separation and purification performance of hydrogen is critical for application of hydrogen energy. In this work, hydrogen separating performance of Pd–Cu and Pd–Ni alloy membranes are theoretically explored through density functional theory and molecular dynamics calculations. The results demonstrate that both Pd–Cu and Pd–Ni membranes exhibit excellent selectivity to H 2 over N 2 , CO, CO 2 , CH 4 , H 2 S at varied temperatures, and are superior to industrial production limit based on predicting permeance of H 2. The outstanding selectivity of Pd–Cu alloy toward H 2 is in accordance with experimental conclusion. Moreover, the DFT calculations are further supported by molecular dynamics simulations, which visually demonstrate the H 2 separation performance of the Pd-based alloys in a dynamic way. This work provides an effective and efficient approach to evaluate the permeability and selectivity of metal alloys membranes for gas separation. • For the first time, hydrogen selectivity and permeance of Pd-alloys are studied. • Selectivity of Pd–Cu alloy membrane to H 2 is much greater than that of Pd–Ni alloy. • The predicted H 2 separation performance of Pd–Cu consists with experiments. • Permeance of H 2 exceed the industrial production limit at various temperatures. • Our method can be used to evaluate permeability and selectivity of alloy membrane. [ABSTRACT FROM AUTHOR]

The complete enzyme catalytic cycle includes substrate binding, chemical reaction and product release, in which different dynamic conformations are adopted. Due to the complex relationship among enzyme activity, stability and dynamics, the directed evolution of enzymes for improved activity or stability commonly leads to a trade-off in stability or activity. It hence remains a challenge to engineer an enzyme to have both enhanced activity and stability. Here, we have attempted to reconstruct the dynamics correlation network involved with active center to improve both activity and stability of a 2,3-butanediol dehydrogenase (2,3-BDH) by introducing inter-chain disulfide bonds. A computational strategy was first applied to evaluate the effect of introducing inter-chain disulfide bond on activity and stability of three 2,3-BDHs, and the N258C mutation of 2,3-BDH from Corynebacterium glutamicum (Cg BDH) was proved to be effective in improving both activity and stability. In the results, Cg BDH-N258C showed a different unfolding curve from the wild type, with two melting temperatures (T m) of 68.3 °C and 50.8 °C, 19.7 °C and 2 °C higher than 48.6 °C of the wild type. Its half-life was also improved by 14.8-fold compared to the wild type. Catalytic efficiency (k cat / K m) of the mutant was increased by 7.9-fold toward native substrate diacetyl and 8.8-fold toward non-native substrate 2,5-hexanedione compared to the wild type. Molecular dynamics simulations revealed that an interaction network formed by Cys258, Arg162, Ala144 and the catalytic residues was reconstructed in the mutant and the dynamics change caused by the disulfide bond could be propagated through the interactions network. This improved the enzyme stability and activity by decreasing the flexibility and locking more "reactive" pose, respectively. Further construction of mutations including A144G showing a 44-fold improvement in catalytic efficiency toward meso -2,3-BD confirmed the role of modifying dynamics correlation network in tunning enzyme activity and selectivity. This study provided important insights into the relationship among dynamics, enzyme catalysis and stability, and will be useful in the designing new enzymes with co-evolution of stability, activity and selectivity. [ABSTRACT FROM AUTHOR]

[Display omitted] • Detailed conformational analysis of solvated l -DOPA in acidic conditions using MD and DFT. • Obtaining state-of-the-art VOA spectra of l -DOPA in an acidic aqueous solution. • Refined conformer ratios based on experimental data, thus improving simulation accuracy. • Paving the way for future research on deuterated l -DOPA analogs. l -DOPA plays a critical role as a precursor to dopamine and is a standard treatment for Parkinson's disease. Recent research has highlighted the potential therapeutic advantages of deuterated l -DOPA analogs having a longer biological half-life. For their spectroscopic characterization, the in-detail characterization of l -DOPA itself is necessary. This article presents a thorough examination of the vibrational spectra of l -DOPA, with a particular emphasis on chirally sensitive VOA techniques. We successfully obtained high-quality Raman and ROA spectra of l -DOPA in its cationic form, under low pH conditions, and at a high concentration of 100 mg/ml. These spectra cover a broad spectral range, allowing for precise comparisons with theoretical simulations. We also obtained IR and VCD spectra, but they faced limitations due to the narrow accessible spectral region. Exploration of l -DOPA's conformational landscape revealed its intrinsic flexibility, with multiple coexisting conformations. To characterize these conformations, we employed two methods: one involved potential energy surface scans with implicit solvation, and the other utilized molecular dynamics simulations with explicit solvation. Comparing ROA spectra from different conformer groups and applying spectral decomposition proved crucial in determining the correct conformer ratios. The use of explicit solvation significantly improved the quality of the final simulated spectral profiles. The accurate determination of conformer ratios, rather than solely relying on the number of averaged spectra, played a crucial role in simulation accuracy. In conclusion, our study offers valuable insights into the structure and conformational behavior of l -DOPA and represents a valuable resource for subsequent spectroscopic studies of its deuterated analogs. [ABSTRACT FROM AUTHOR]

• Four thieno[2,3- d ]pyrimidines were synthesized as VEGFR-2 inhibitors. • VEGFR-2 inhibition and cytotoxicity against HepG-2 and MCF-7 cells were evaluated. • Mechanistic studies as apoptosis, cell cycle, Bcl-2, caspase-8, and caspase-9 levels were assessed. • In silico docking, MD simulations, DFT, ADMET, and toxicity studies were performed. Angiogenesis is a critical regulatory mechanism for tumor development and metastasis. Tumor growth is closely related to the production of the vascular endothelial growth factor (VEGF), which is mediated by the cell-surface kinase VEGFR-2. Accordingly, blocking of VEGFR-2 is an important approach to find new treatments for malignancies. The aim of this research is the synthesis of new thieno[2,3- d ]pyrimidine derivatives that could be potential anticancer leads inhibiting VEGFR-2. The prepared thieno[2,3- d ]pyrimidine derivatives were tested in vitro for their inhibitory effects against the kinase activity of VEGFR-2. In addition, the synthesized compounds were assessed for their anti-proliferative activities against MCF-7 and HepG2 cell lines. Compound 4c displayed the strongest anti-VEGFR-2 potentiality with an IC 50 value of 0.15 µM and exhibited good anti-proliferative effects against HepG2 and MCF-7 cells with IC 50 of 17.14 and 11.56 µM, respectively. Compound 4c induced cell cycle arrest at the S phase and boosted early and late apoptosis in MCF-7 cells. Additionally, compound 4c increased BAX (4.5-fold), decreased Bcl-2 (3.5-fold), and demonstrated a notable increase in caspase-8 (2.9-fold) and caspase-9 (3.3-fold) levels. Furthermore, compound 4c significantly reduced TNF-α (3.6-fold) and IL-6 (3.2-fold) levels in MCF-7 cells. Molecular docking studies indicated good binding affinities as well as energies of the thieno[2,3- d ]pyrimidine derivatives against the VEGFR-2. Molecular dynamics (MD) simulations were utilized to study the structural, energetic, and conformational changes of the VEGFR-2– 4c complex, and the results indicated its stability. The MM-GBSA study of the VEGFR-2– 4c complex showed a stable thermodynamic behavior with a binding free energy of -44 kcal/mol. The PLIP analysis identified the 3D interactions and binding conformation through the VEGFR-2– 4c complex. Moreover, the DFT studies have been performed to study, Mullikan atomic charge distribution, FMO, ESP, the total density of state, and the QTAIM maps of compound 4c to theoretically verify its reactivity. Finally, computational ADMET and toxicity studies were conducted to assess the drug development potential of the thieno[2,3- d ]pyrimidine derivatives. [Display omitted] [ABSTRACT FROM AUTHOR]

Successful decoding of structural descriptors controlling the crystallization in multicomponent functional glasses can pave the way for the transition from the trial-and-error approach and empirical modeling for glass/glass-ceramic composition design toward more rational and scientifically rigorous Quantitative Structure-Property Relationship (QSPR) based models. However, due to the compositional and structural complexity of multicomponent glasses and the longer time and length scales associated with nucleation, the development and validation of QSPR models are still in it's infancy. The work presented in the article is an attempt to leap forward in this pursuit by combining the strengths of experimental and computational materials science to decode the chemo-structural drivers that promote or suppress nucleation and crystal growth in alkali/alkaline-earth aluminoborosilicate glasses leading to the development of a QSPR-based model (powered by MD simulations). The results reveal the following two descriptors that govern the nucleation and crystallization of a particular aluminosilicate phase in the functional glasses: (1) degree of mixing between the SiO 4 and AlO 4 units, i.e., Si–O–Al linkages, and (2) difference/similarity between the short-to-intermediate range ordering in the glass structure to that of the structure of corresponding crystalline phase. Based on the established composition–structure–crystallization behavior relationships, a cluster analysis based QSPR model has been developed (and tested) to predict the propensity of nepheline (and anorthite) crystallization in the investigated glasses. The model has been tested on several compositions from the present and previous studies and has successfully predicted the crystallization propensity of all glass compositions, even in cases where previous empirical and semi-empirical models were unsuccessful. [Display omitted] [ABSTRACT FROM AUTHOR]

Redox reactions in living cells involving a coenzyme nicotinamide-adenine-dinucleotide (NAD) are stereospecific and depend on NAD conformation states and on the structure of enzyme binding sites. Therefore, information on NAD conformation states in various environments is important for understanding of the mechanisms of redox reactions. In this paper the structural dynamics of reduced nicotinamide-adenine-dinucleotide (NADH) in water–methanol and water–ethanol solutions was investigated by means of molecular dynamics simulations. The trajectory analysis revealed three stable conformation groups characterized by the distance R N A − A D between adenine and nicotinamide centers of mass: folded ( R N A − A D < 5.5 Å), intermediate (5.5 Å < R N A − A D < 12 Å) and unfolded ( R N A − A D > 12 Å). It was shown that conformation equilibrium shifted from the folded conformation group at low alcohol concentrations towards the intermediate conformation group at high alcohol concentrations, while the fractional concentration of unfolded conformation group remained almost constant. The nicotinamide and adenine rings were found to be almost parallel in folded conformations and perpendicular in intermediate conformations, while no preferable positions of the rings were found in unfolded conformations. The results obtained were used for the analysis of experimentally determined rotational diffusion times τ r e x p in NADH in water–methanol and water–ethanol mixtures. Comparison between the calculated and experimental τ r values using the generalized Stokes–Einstein–Debye equation allowed for determination of the wettability coefficient C and effective molecular volume V m as a function of alcohol concentration. The coefficient C was found to be always less than unity and have a minimum at 40% of alcohol which was more pronounced for ethanol than for methanol mixtures. This dependence was attributed to the influence of solution viscosity that has a maximum at 40% of alcohol. The effective molecular volume V m was found to be practically constant at alcohol concentrations below 60% and rise dramatically at higher alcohol concentrations. This dependence was attributed to the solvation of NADH at high alcohol concentrations. [Display omitted] • NADH conformations in water-methanol and water-ethanol mixtures can be separated into three main groups. • Concentration of NADH conformation groups depends on micro-environmental conditions. • MD simulations allowed to analyze the features of NADH rotational diffusion. [ABSTRACT FROM AUTHOR]

Epoxy resins are extensively used as the matrix for carbon-fiber-reinforced plastic (CFRP) in commercial airplanes due to their outstanding thermomechanical properties. Until now, few researchers have simulated multicomponent epoxy resins. In this work, the impact of stoichiometric variations in the base resins in the Di Glycidyl Ether of Bisphenol A (DGEBA)/Tetra Glycidyl Diamino Diphenyl Methane (TGDDM)/4,4′-Diamino Diphenyl Sulfone (4,4′-DDS) system on the curing process and thermomechanical properties is investigated. When the proportions of each component are comparable, the curing process is primarily determined initially by the component with a lower activation energy and subsequently by the component with a relatively greater quantity during the high conversion rate stage. Furthermore, a higher proportion of TGDDM in the DGEBA/TGDDM/4,4′-DDS system results in an increased number of ring structures, which in turn leads to enhanced thermomechanical properties. Our Python-LAMMPS algorithm can be further developed for designing new multi-component epoxy resin materials. [Display omitted] • Multi-component crosslinked epoxy resin systems were constructed based on our curing reaction model. • The competition mechanism of reactive epoxy components in the crosslinking process was investigated. • The relationship between thermomechanical properties and the internal structure of multi-component systems was uncovered. [ABSTRACT FROM AUTHOR]

Brevicoryne brassicae , an aphid species, exclusively consumes plants from the Brassicaceae family and employs a sophisticated defense mechanism involving a myrosinase enzyme that breaks down glucosinolates obtained from its host plants. In this work, we employed combined quantum mechanical and molecular mechanical (QM/MM) calculations and molecular dynamics (MD) simulations to study the catalytic reaction of aphid myrosinase. A proper QM region to study the myrosinase reaction should contain the whole substrate, models of Gln-19, His-122, Asp-124, Asn-166, Glu-167, Lys-173, Tyr-180, Val-228, Tyr-309, Tyr-346, Ile-347, Glu-374, Glu-423, Trp-424, and a water molecule. The calculations show that Asp-124 and Glu-423 must be charged, His-122 must be protonated on NE2, and Glu-167 must be protonated on OE2. Our model reproduces the anomeric retaining characteristic of myrosinase and indicates that the deglycosylation reaction is the rate-determining step of the reaction. Based on the calculations, we propose a reaction mechanism for aphid myrosinase-mediated hydrolysis of glucosinolates with an overall barrier of 15.2 kcal/mol. According to the results, removing a proton from Arg-312 or altering it to valine or methionine increases glycosylation barriers but decreases the deglycosylation barrier. The proposed computational-based mechanism for aphid myrosinase unveils novel insights into its catalytic process using QM/MM modeling. [Display omitted] [ABSTRACT FROM AUTHOR]