Computer-aided mining of a psychrophilic cellobiose 2-epimerase from the Qinghai-Tibet Plateau gene catalogue.

Cellobiose 2-epimerase (CE) catalyzes the conversion of the lactose into its high-value derivatives, epilactose and lactulose, which has great prospects in food applications. In this study, CE sequences from the Qinghai-Tibet Plateau gene catalogue, we screened these for structural flexibility through molecular dynamics simulation to identify potential psychrophilic CE candidates. One such psychrophilic CE we termed psyCE demonstrated exceptional epimerization activity, achieving an optimum activity of 122.2 ± 1.6 U/mg. Its kinetic parameters (Kcat and Km) for epimerization activity were 219.9 ± 5.6 s-1 and 261.9 ± 18.1 mM, respectively, representing the highest Kcat recorded among known cold-active CEs. Notably, this is the first report of a psychrophilic CE. The psyCE can effectively produce epilactose at 8 °C, converting 20.3 % of 200 mM lactose into epilactose within four hours. These findings suggest that psyCE is highly suitable for cryogenic food processing, and glaciers may serve as a valuable repository of psychrophilic enzymes.

Design, synthesis and anti-HBV activity study of novel HBV capsid assembly modulators.

Capsid assembly modulators (CAMs) have the potential to cure chronic hepatitis B, as demonstrated in clinical trials. Lead compounds NVR3-778 and 5a were found to exist in normal and flipped conformations through induced fit docking. Therefore, we designed and synthesized series I and II compounds by interchanging the amide and sulfonamide bonds of 5a to modify both the tolerance region and solvent-opening region. Among them, compound 4a (EC50 = 0.24 ±â€¯0.10 µM, CC50 > 100 µM) exhibited potent anti-HBV activity with low toxicity, surpassing the lead compounds NVR3-778 (EC50 = 0.29 ±â€¯0.03 µM, CC50 = 20.78 ±â€¯2.29 µM) and 5a (EC50 = 0.50 ±â€¯0.07 µM, CC50 = 48.16 ±â€¯9.15 µM) in HepAD38 cells. Additionally, compared with the lead compound, 4a displayed a stronger inhibitory effect on HBV capsid protein assembly. Molecular dynamics (MD) simulations confirmed that the normal conformation of 4a had relatively stable conformation at different frames of binding modes. Furthermore, 4a showed better metabolic stability in human plasma than positive control drugs. Therefore, compound 4a could be further structurally modified as a potent lead compound.

Inhibition of Lysosomal Cathepsin A and Neuraminidase 1 Interaction by Anti-obesity Cyclic Peptide.

Chronic inflammation in adipose tissue is associated with metabolic disorders such as obesity and type 2 diabetes. Novel small molecules targeting adipocyte differentiation and fat accumulation offer potential for new anti-inflammatory and anti-obesity drugs. Here we show that the marine cyclic heptapeptide stylissatin A and its analogs (SAs) inhibit membranous neuraminidase 1 (Neu1) function by interacting with lysosomal protective protein cathepsin A (PPCA). Neu1 has been less explored as a therapeutic target due to the genetic defects leading to neurodegenerative disorders. However, unlike traditional neuraminidase inhibitors, SAs don't directly bind to Neu1 but modulate the molecular chaperone activity of PPCA. SAs caused degradation of perilipin 1 around lipid droplets and inhibited fat accumulation, along with decrease in membranous Neu1. Molecular docking and molecular dynamics simulations revealed that SAs interacted with activated PPCA at the Neu1 binding site. Focusing on this newfound protein-protein interaction inhibition mechanism could lead to the development of pharmaceuticals with fewer side effects.

Structural Characterization of DNA Binding Domain of Essential Mammalian Protein TTF 1.

Transcription Termination Factor 1 (TTF1) is a multifunctional mammalian protein with vital roles in various cellular processes, including Pol I-mediated transcription initiation and termination, pre-rRNA processing, chromatin remodelling, DNA damage repair, and polar replication fork arrest. It comprises of two distinct functional regions; the N-terminal regulatory region (1-445 aa), and the C-terminal catalytic region (445-859 aa). The Myb domain located at the C-terminal region is a conserved DNA binding domain spanning from 550 to 732 aa (183 residues). Despite its critical role in various cellular processes, the physical structure of TTF1 remains unsolved. Attempts to purify the functional TTF1 protein have been unsuccessful till date. Therefore, we focused on characterizing the Myb domain of this essential protein. We started with predicting a 3-D model of the Myb domain using homology modelling, and ab-initio method.  We then determined its stability through MD simulation in an explicit solvent. The model predicted is highly stable, which stabilizes at 200ns. To experimentally validate the computational model, we cloned and expressed the codon optimized Myb domain into a bacterial expression vector and purified the protein to homogeneity. Further, characterization of the protein shows that, Myb domain is predominantly helical (65%) and is alone sufficient to bind the Sal Box DNA. This is the first-ever study to report a complete in-silico model of the Myb domain, which is physically characterized. The above study will pave the way towards solving the atomic structure of this essential mammalian protein.

Molecular dynamics simulation of DNAN/DNB cocrystal PBXs.

CONTEXT: The DNAN/DNB eutectic is a high-energy explosive eutectic with superior safety and thermal stability compared to traditional melt-cast explosives. However, the addition of polymer binders can effectively enhance its mechanical properties, allowing for continued production demands without the need for changes to existing factory equipment. In this paper, a model of the DNAN/DNB eutectic explosive was established, and five different types of polymers-cis-1,4-polybutadiene (BR), ethylene-vinyl acetate copolymer (EVA), polyethylene glycol (PEG), fluorinated polymer (F2603), and polyvinylidene fluoride (PVDF)-were added to the (1 0 - 1), (1 0 1), and (0 1 1) cleavage planes, respectively, to form polymer-bonded explosives (PBXs). The stability, trigger bond length, mechanical properties, and detonation performance of the various polymer-bound PBXs were predicted retrogressively. Among the five PBX models, the DNAN/DNB/PEG model exhibited the highest binding energy and the shortest trigger bond length, indicating a significant improvement in stability, compatibility, and sensitivity compared to the original eutectic. Additionally, although the detonation performance of DNAN/DNB decreased after the addition of binders, the final results were still satisfactory. Overall, the DNAN/DNB/PEG model demonstrated excellent comprehensive performance, proving that among the many polymer binders, PEG is the optimal choice for DNAN/DNB. METHODS: Within the Materials Studio software, molecular dynamics (MD) simulations were employed to predict the properties of the DNAN/DNB eutectic PBX. The MD simulation timestep was set to 1 fs, with a cumulative simulation duration of 2 ns. A 2 ns MD simulation was conducted using the isothermal-isobaric ensemble (NPT). The COMPASS force field was applied, and the temperature was fixed at 295 K.

Network pharmacology and molecular dynamics study of the effect of the Astragalus-Coptis drug pair on diabetic kidney disease.

BACKGROUND: Diabetic kidney disease (DKD) is the primary cause of end-stage renal disease. The Astragalus-Coptis drug pair is frequently employed in the management of DKD. However, the precise molecular mechanism underlying its therapeutic effect remains elusive. AIM: To investigate the synergistic effects of multiple active ingredients in the Astragalus-Coptis drug pair on DKD through multiple targets and pathways. METHODS: The ingredients of the Astragalus-Coptis drug pair were collected and screened using the TCMSP database and the SwissADME platform. The targets were predicted using the SwissTargetPrediction database, while the DKD differential gene expression analysis was obtained from the Gene Expression Omnibus database. DKD targets were acquired from the GeneCards, Online Mendelian Inheritance in Man database, and DisGeNET databases, with common targets identified through the Venny platform. The protein-protein interaction network and the "disease-active ingredient-target" network of the common targets were constructed utilizing the STRING database and Cytoscape software, followed by the analysis of the interaction relationships and further screening of key targets and core active ingredients. Gene Ontology (GO) function and Kyoto Ency-clopedia of Genes and Genomes (KEGG) pathway enrichments were performed using the DAVID database. The tissue and organ distributions of key targets were evaluated. PyMOL and AutoDock software validate the molecular docking between the core ingredients and key targets. Finally, molecular dynamics (MD) simulations were conducted to simulate the optimal complex formed by interactions between core ingredients and key target proteins. RESULTS: A total of 27 active ingredients and 512 potential targets of the Astragalus-Coptis drug pair were identified. There were 273 common targets between DKD and the Astragalus-Coptis drug pair. Through protein-protein interaction network topology analysis, we identified 9 core active ingredients and 10 key targets. GO and KEGG pathway enrichment analyses revealed that Astragalus-Coptis drug pair treatment for DKD involves various biological processes, including protein phosphorylation, negative regulation of apoptosis, inflammatory response, and endoplasmic reticulum unfolded protein response. These pathways are mainly associated with the advanced glycation end products (AGE)-receptor for AGE products signaling pathway in diabetic complications, as well as the Lipid and atherosclerosis. Molecular docking and MD simulations demonstrated high affinity and stability between the core active ingredients and key targets. Notably, the quercetin-AKT serine/threonine kinase 1 (AKT1) and quercetin-tumor necrosis factor (TNF) protein complexes exhibited exceptional stability. CONCLUSION: This study demonstrated that DKD treatment with the Astragalus-Coptis drug pair involves multiple ingredients, targets, and signaling pathways. We propose a novel approach for investigating the molecular mechanism underlying the therapeutic effects of the Astragalus-Coptis drug pair on DKD. Furthermore, we suggest that quercetin is the most potent active ingredient and specifically targets AKT1 and TNF, providing a theoretical foundation for further exploration of pharmacologically active ingredients and elucidating their molecular mechanisms in DKD treatment.

Multiscale simulations of DNA from electrons to nucleosomes: 22 years of the Ascona B-DNA Consortium.

This commentary provides a retrospective on the Ascona B-DNA Consortium (ABC) initiative and on the conference held in April 2023 at Ascona, Switzerland, where we celebrated 22 years of the consortium, sharing the latest advances in simulations and experiments of the effects of sequence on the mechanical properties of DNA from electrons to nucleosomes.

DNA damage and repair in the nucleosome: insights from computational methods.

Cellular DNA is constantly exposed to endogenous or exogenous factors that can induce lesions. Several types of lesions have been described that can result from UV/ionizing irradiations, oxidative stress, or free radicals, among others. In order to overcome the deleterious effects of such damages, i.e., mutagenicity or cytotoxicity, cells possess a highly complex DNA repair machinery, involving repair enzymes targeting specific types of lesions through dedicated cellular pathways. In addition, DNA is highly compacted in the nucleus, the first level of compaction consisting of ~ 147 DNA base pairs wrapped around a core of histones, the so-called nucleosome core particle. In this complex environment, the DNA structure is highly constrained, and fine-tuned mechanisms involving remodeling processes are required to expose the DNA to repair enzymes and to facilitate the damage removal. However, these nucleosome-specific mechanisms remain poorly understood, and computational methods emerged only recently as powerful tools to investigate DNA damages in such complex systems as the nucleosome. In this mini-review, we summarize the latest advances brought out by computational approaches in the field, opening new exciting perspectives for the study of DNA damage and repair in the nucleosome context.

On the solubility of azodicarbonamide in water/DMSO mixtures: an experimental and computational study.

This work aims at studying why azodicarbonamide (ADCA), a formally apolar compound with good hydrogen bond (HB) acceptors, is soluble only in polar aprotic solvents like dimethyl sulfoxide (DMSO) but not in water. Solubility measurements, as well as quantum mechanical and classical molecular dynamics simulations, were employed to tackle the problem. We found that in the liquid phase a polar conformer of ADCA (µ = 8.7 D), unreported to date, is favoured under the enthalpic drive provided by a highly polar solvent. At the same time, the very high hydrogen bond propensity of water with itself prevents this solvent from providing an effective hydrogen bond-mediated solvation. Solvents bearing good HB acceptors, while lacking strong HB donors, contribute to further stabilizing solute-solvent adducts through weak and fluxional HBs that involve the amide groups of ADCA. Implications for the solubility of ADCA down to µM concentrations were evaluated, also with the aid of classical simulations of solution nanodroplets.

Insights on the comparative affinity of ribonucleic acids with plant-based beta carboline alkaloid, harmine: Spectroscopic, calorimetric and computational evaluation.

Small molecules as ligands target multifunctional ribonucleic acids (RNA) for therapeutic engagement. This study explores how the anticancer DNA intercalator harmine interacts various motifs of RNAs, including the single-stranded A-form poly (rA), the clover leaf tRNAphe, and the double-stranded A-form poly (rC)-poly (rG). Harmine showed the affinity to the polynucleotides in the order, poly (rA) > tRNAphe > poly (rC)·poly (rG). While no induced circular dichroism change was detected with poly (rC)poly (rG), significant structural alterations of poly (rA) followed by tRNAphe and occurrence of concurrent initiation of optical activity in the attached achiral molecule of alkaloid was reported. At 25 °C, the affinity further showed exothermic and entropy-driven binding. The interaction also highlighted heat capacity (ΔC o p ) and Gibbs energy contribution from the hydrophobic transfer (ΔG hyd) of binding with harmine. Molecular docking calculations indicated that harmine exhibits higher affinity for poly (rA) compared to tRNAphe and poly (rC)·poly (rG). Subsequent molecular dynamics simulations were conducted to investigate the binding mode and stability of harmine with poly(A), tRNAphe, and poly (rC)·poly (rG). The results revealed that harmine adopts a partial intercalative binding with poly (rA) and tRNAphe, characterized by pronounced stacking forces and stronger binding free energy observed with poly (rA), while a comparatively weaker binding free energy was observed with tRNAphe. In contrast, the stacking forces with poly (rC)·poly (rG) were comparatively less pronounced and adopts a groove binding mode. It was also supported by ferrocyanide quenching analysis. All these findings univocally provide detailed insight into the binding specificity of harmine, to single stranded poly (rA) over other RNA motifs, probably suggesting a self-structure formation in poly (rA) with harmine and its potential as a lead compound for RNA based drug targeting.

Dataset of simulated vibrational density of states and X-ray diffraction profiles of mechanically deformed and disordered atomic structures in Gold, Iron, Magnesium, and Silicon.

This dataset is comprised of a library of atomistic structure files and corresponding X-ray diffraction (XRD) profiles and vibrational density of states (VDoS) profiles for bulk single crystal silicon (Si), gold (Au), magnesium (Mg), and iron (Fe) with and without disorder introduced into the atomic structure and with and without mechanical loading. Included with the atomistic structure files are descriptor files that measure the stress state, phase fractions, and dislocation content of the microstructures. All data was generated via molecular dynamics or molecular statics simulations using the Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) code. This dataset can inform the understanding of how local or global changes to a materials microstructure can alter their spectroscopic and diffraction behavior across a variety of initial structure types (cubic diamond, face-centered cubic (FCC), hexagonal close-packed (HCP), and body-centered cubic (BCC) for Si, Au, Mg, and Fe, respectively) and overlapping changes to the microstructure (i.e., both disorder insertion and mechanical loading).

Molecular simulation of the slurrying mechanism in microplastic semi-coke water slurry.

CONTEXT: This study explores the interaction between particles in microplastic semi-coke water slurry at the molecular level using molecular simulation methods, specifically DFT calculations and MD simulations. In addition, the experiment of slurry preparation was carried out to study the viscosity and stability of the slurry. The electrostatic potential analysis shows that the interaction between microplastics and dispersant molecules occurs on atoms with large electronegativity or oxygen-containing functional groups, and the energy gap of frontier molecular orbitals indicated that PVC interacts most easily with the dispersant (0.39 eV), followed by PS (1.08 eV) and PET (3.65 eV). In addition, it is also noted that due to the steric hindrance effect, the adsorption energy was opposite to the DFT calculation results: PET was - 213.338 kcal/mol (NNO) which was highest, followed by PS (- 107.603 kcal/mol, NNO), and PVC (NNO) was lowest which was - 94.808 kcal/mol. And RDF shows similar results, which the probability of water molecules in the PET system was the highest, followed by PS, and finally, PVC. The MD results are consistent with the viscosity and stability characterization results of the slurry which PET has the lowest viscosity of 87.3 mPa·s. Finally, this study provides new ideas for the treatment of microplastics and the improvement of the performance of semi-coke water slurry and reveals the interaction mechanism between microplastics and semi-coke water slurry. METHODS: All calculations were performed using Materials Studio (MS) version 2020 software, BIOVIA Corporation. The DFT calculation was carried out through the DMol3 module. The DFT calculations include electron density, electrostatics, orbitals, and population analysis. In DMol3 module, the GGA-PBE function was selected to consider gradient changes in density in the simulated calculation. The DFT-D correction was selected, and all electrons were calculated by DNP for accurate core potentials and the DNP file was 4.4. MD simulation was performed through the Forcite module. MD simulation mainly focuses on relative concentration distribution analysis, radial distribution function, and adsorption energy calculation. All molecular geometry optimizations are performed in the Forcite module. In the molecular dynamic part, all simulations used PCFF forcefield. The NVT ensemble was adopted and using the Nosé thermostat.

Molecular dynamics simulations for the structure-based drug design: targeting small-GTPases proteins.

INTRODUCTION: Molecular Dynamics (MD) simulations can support mechanism-based drug design. Indeed, MD simulations by capturing biomolecule motions at finite temperatures can reveal hidden binding sites, accurately predict drug-binding poses, and estimate the thermodynamics and kinetics, crucial information for drug discovery campaigns. Small-Guanosine Triphosphate Phosphohydrolases (GTPases) regulate a cascade of signaling events, that affect most cellular processes. Their deregulation is linked to several diseases, making them appealing drug targets. The broad roles of small-GTPases in cellular processes and the recent approval of a covalent KRas inhibitor as an anticancer agent renewed the interest in targeting small-GTPase with small molecules. AREA COVERED: This review emphasizes the role of MD simulations in elucidating small-GTPase mechanisms, assessing the impact of cancer-related variants, and discovering novel inhibitors. EXPERT OPINION: The application of MD simulations to small-GTPases exemplifies the role of MD simulations in the structure-based drug design process for challenging biomolecular targets. Furthermore, AI and machine learning-enhanced MD simulations, coupled with the upcoming power of quantum computing, are promising instruments to target elusive small-GTPases mutations and splice variants. This powerful synergy will aid in developing innovative therapeutic strategies associated to small-GTPases deregulation, which could potentially be used for personalized therapies and in a tissue-agnostic manner to treat tumors with mutations in small-GTPases.

Deciphering the multi-target therapeutic capabilities of Ocimum tenuiflorum Linn. Compounds against systemic lupus erythematosus and inflammatory bowel disease: a network pharmacology and molecular modelling approach.

The coexistence of Systemic Lupus Erythematosus (SLE) and Inflammatory Bowel Disease (IBD) is a rare and hard-to-diagnose multisystem autoimmune disorder. Allopathic treatment approaches often fall short in managing both conditions simultaneously, as specific medications targeting this dual manifestation are lacking. In such instances, herbal medicine can offer a potential solution through its holistic approach. Ocimum tenuiflorum (O. tenuiflorum) a rich source of bioactive compounds belonging to Lamiaceae family. This study employs network pharmacology and molecular modelling to unveil the multi-target and multi-pathway mechanisms of O. tenuiflorum as a complementary therapy. A total of 423 common targets were obtained, among which AKT1, TNF, SRC, EGFR, HIF1A, HSP9AA, BCL2, and STAT3 were identified as the key targets. Lastly, molecular modelling validated the strong binding affinity between O. tenuiflorum 's compounds and the identified targets. In conclusion, these investigations provide new insight for further study of O. tenuiflorum towards the management of SLE and IBD.

Unveiling the Mechanism of Spontaneous Nanoscroll Formation from Janus Transition Metal Dichalcogenide Nanoribbons.

Due to the atomic asymmetry, Janus transition metal dichalcogenide monolayers possess spontaneous curling and can even form one-dimensional nanoscrolls. Unveiling this spontaneous formation mechanism of nanoscrolls is of great importance for precise structural control. In this paper, we successfully simulate the process of Janus MoSSe nanoscroll formation from flat nanoribbons, based on molecular dynamics (MD) simulations with hybrid potentials. The spontaneous scrolling is purely driven by the relaxation of intrinsic strain in Janus MoSSe. The final structure of nanoscroll is strongly affected by the length of nanoribbon with a nonmonotonous relation. To further understand the mechanism, we establish a thermodynamic model to determine the inner radius of MoSSe nanoscrolls, which is shown to be related to spontaneous curvature, bending stiffness, interlayer van der Waals interaction, interlayer distance, and length of initial nanoribbon. The results correspond well with MD simulations of nanoscrolls from flat nanoribbons and the molecular static simulations of directly built nanoscrolls. Moreover, the inner radii of MoSeTe and MoSTe nanoscrolls are predicted based on the model. Our results provide insights into the Janus TMD nanoscroll formation and a pathway for controllable fabrication of nanoscrolls.

Revealing the principles of inter- and intra-domain regulation in a signaling enzyme via scanning mutagenesis.

Multi-domain enzymes can be regulated by both inter-domain interactions and structural features intrinsic to the catalytic domain. The tyrosine phosphatase SHP2 is a quintessential example of a multi-domain protein that is regulated by inter-domain interactions. This enzyme has a protein tyrosine phosphatase (PTP) domain and two phosphotyrosine-recognition domains (N-SH2 and C-SH2) that regulate phosphatase activity through autoinhibitory interactions. SHP2 is canonically activated by phosphoprotein binding to the SH2 domains, which causes large inter-domain rearrangements, but autoinhibition can also be disrupted by disease-associated mutations. Many details of the SHP2 activation mechanism are still unclear, the physiologically-relevant active conformations remain elusive, and hundreds of human variants of SHP2 have not been functionally characterized. Here, we perform deep mutational scanning on both full-length SHP2 and its isolated PTP domain to examine mutational effects on inter-domain regulation and catalytic activity. Our experiments provide a comprehensive map of SHP2 mutational sensitivity, both in the presence and absence of inter-domain regulation. Coupled with molecular dynamics simulations, our investigation reveals novel structural features that govern the stability of the autoinhibited and active states of SHP2. Our analysis also identifies key residues beyond the SHP2 active site that control PTP domain dynamics and intrinsic catalytic activity. This work expands our understanding of SHP2 regulation and provides new insights into SHP2 pathogenicity.

Water/oil interfacial behaviors of soy hull polysaccharide revealed by molecular dynamics simulation and particle tracking microrheology.

The soy hull polysaccharide (SHP) exhibits excellent interfacial activity and holds potential as an emulsifier for emulsions. To reveal the behavior of SHP at the water/oil (W/O) interface in situ, molecular dynamics (MD) simulations and particle tracking microrheology were used in this study. The results of MD reveal that SHP molecular spontaneously move toward the interface and rhamnogalacturonan-I initiates this movement, while its galacturonic acids on it act as anchors to immobilize the SHP molecules at the W/O interface. Microrheology results suggest that SHP forms microgels at the W/O interface, with the lattices of the microgels continually undergoing dynamic changes. At low concentrations of SHP and short interfacial formation time, the network of the microgels is weak and dominated by viscous properties. However, when SHP reaches 0.75 % and the interfacial formation time is about 60 min, the microgels show perfect elasticity, which is beneficial for stabilizing emulsions.

From waste to wonder: exploring the hypoglycemic and anti-oxidant properties of corn processing by-products.

Introduction: The industrial processing of corn (Zeamays L.) generates by-products such as corn silk, straw peels, and straw core, which contribute to adverse environmental impacts. Our study aimed to investigate sustainable approaches for mitigating these effects by evaluating the hypoglycemic potential and mechanisms of ethyl acetate fractions derived from these corn derivatives. Methods: We employed glucose consumption assays, high glucose stress tests, UPLC-QE-Orbitrap-MS analysis, molecular docking, and simulations to assess their components and efficacy. Antioxidant capacities were evaluated using DPPH, FRAP, ABTS, and •OH scavenging assays. Results: Notably, the ethyl acetate fraction extracted from straw peels (SPE) exhibited a high concentration of flavonoids and phenolic compounds along with pronounced hypoglycemic activity and antioxidant capacity. SPE significantly enhanced glucose consumption in insulin-resistant HepG2 cells while protecting HUVECs against damage caused by high glucose levels. Molecular docking analyses confirmed the interaction between active compounds and α-glucosidase as well as α-amylase, while molecular dynamic simulations indicated stability at their binding sites. Discussion: In conclusion, the hypoglycemic and antioxidative properties observed in corn by-products such as straw peels, corn silk, and straw core can be attributed to the inhibition of α-glucosidase and α-amylase activities, coupled with their rich phenolic and flavonoid content. These findings highlight the potential of these by-products for applications in healthcare management and their sustainable utilization, demonstrating significant value in the use of agricultural residues.

A novel ACE inhibitory peptide from Douchi hydrolysate: Stability, inhibition mechanism, and antihypertensive potential in spontaneously hypertensive rats.

Angiotensin I-converting enzyme (ACE) regulates blood pressure through the renin-angiotensin system. Douchi, a traditional fermented soybean condiment, may have antihypertensive effects, but research on ACE inhibitory peptides from Douchi hydrolysates is limited. We hypothesized that enzymatic treatment could enhance ACE inhibitory peptide diversity and efficacy. We tested ten single enzymes and four combinations, finding pepsin-trypsin-chymotrypsin most effective. Hydrolysates were purified using Sephadex G-15 and reversed-phase HPLC, and peptides were identified via LC-MS/MS. Five peptides (LF, VVF, VGAW, GLFG, NGK) were identified, with VGAW as the most potent ACE inhibitor (IC50 46.6 ± 5.2 µM) showing excellent thermal and pH stability. Lineweaver-Burk plots confirmed competitive inhibition, and molecular docking revealed eight hydrogen bonds between VGAW and ACE. In hypertensive rats, VGAW significantly reduced blood pressure at 12.5, 25, and 50 mg/kg. These findings highlight Douchi as a source of ACE inhibitory peptides and suggest VGAW as a promising functional food ingredient.

Simulation-based research on enhancing lubricity: investigating wettability and textured surfaces in alkane lubricants under boundary lubrication conditions.

Changing the wettability and surface texturing have a significant impact on lubrication. In this study, the researchers used the molecular dynamics (MD) method to investigate how adjusting the interaction between alkanes and the wall affects oil film morphology and frictional properties under boundary lubrication. The findings revealed that the bearing capacity was influenced by both the morphology of the oil film and the strength of solid-liquid adsorption. In cases where the walls had weak wettability, the alkanes formed clusters to effectively separate the walls, while in cases where the walls had strong wettability, the oil film spread and formed a strong adsorption film. The super oleophilic textured surface could enhance the oil film adsorption capacity and replenish the oil film to the friction area in time, and the super oleophobic smooth surface could further reduce the friction coefficient. Therefore, a composite surface consisting of a super oleophilic textured surface and a super oleophobic smooth surface can be designed to enhance the bearing capacity of the oil film and reduce friction.