Study Of Dynamics Research Articles

Design of New Benzimidazole‐Indazole Derivatives as Potential FLT3 Inhibitors Using 3D‐QSAR, ADMET, Molecular Docking, MM‐GBSA, and Molecular Dynamics Studies

AbstractIn this work, we performed a 3D‐QSAR study on a dataset of benzimidazole‐indazole‐derived molecules reported as FLT3 inhibitors for the treatment of acute myeloid leukemia (AML). This study led to the design of six new molecules with better FLT3 inhibitory activity than the reference inhibitor (gilteritinib) and the synthesized template molecule (M20). The designed molecules are screened for their drug‐like and ADMET proprieties. The obtained results enabled us to select three molecules as the best candidate FLT3 inhibitors. Molecular docking and MM‐GBSA calculations show that the three molecules are more localized and targeted in the FLT3 active site compared to gilteritinib and M20 molecules. Through molecular dynamics simulations, the insertion of the three designed molecules in the FLT3 active site leads to stable complexes during the simulation period. Finally, the three newly designed molecules represent an interesting proposal for the development of drugs against AML.

Exploring the anti-diabetic activity of 2,6-diamino-4-chloropyrimidinium-hydrogen oxalate conjugates: Synthesis, crystal structure, quantum computational, drug-likeness, molecular docking and dynamics simulation

Inhibiting carbohydrate-hydrolyzing enzyme has been considered as an effective approach for controlling starch digestion and postprandial blood glucose level. The aim of this study, the salt molecule was prepared to identify potentially effective compound against diabetic activity and discover the inhibitory mechanism of the targeted enzyme, which is determined by In-silico techniques. And also perform the quantum chemical calculation to provide insights about the internal motions of the molecule at the atomic level. The 2,6-diamino-4-chloropyrimidinium-hydrogen oxalate (C4H6ClN4+. C2HO4-) was newly synthesized molecule, which is detailly discussed in this present work. The title compound has been confirmed by single-crystal X-ray diffraction studies, and this structure was refined by the least-square refinement method. The crystal compound exhibited the P-1 space group (centrosymmetric) and the following unit cell parameters: a = 5.5778(6)Å, b = 9.6687(10)Å, c = 9.9144(10)Å, α = 116.342(1) °, β = 92.610(1) °, γ = 106.370(1) °, Z = 2. The molecular structure is stabilized by the networks of N–H···O, O–H···O, C–H···O, and N–H···N hydrogen bond interactions. The Hirshfeld surface (HS) analysis and fingerprint plots revealed strong intermolecular interaction between the molecules. The structural optimization, frontier molecular orbital (FMO), molecular reactivity, molecular electrostatic potential (MEP), and mulliken atomic charges were generated by the density functional theory (DFT) calculated at B3LYP/6-311G++ (d,p) theory level. Drug-likeness and physicochemical properties were predicted. The molecular docking analysis was showed a binding energy of −8.96 kcal/mol within the active site of alpha-amylase, which is responsible for anti-diabetic activity. The protein-ligand complex stability was verified using molecular dynamics studies with 100 ns.

LC-MS and GC-MS Analyses on Green Algae Penicillus Capitatus: Cytotoxic, Antimicrobial and Anticholinesterase Activity Screening Enhanced by Molecular Docking & Dynamics and ADME Studies.

In this comprehensive screening study, the chemical composition, and cytotoxic, antimicrobial, and anticholinergic activities of the green algae Penicillus capitatus, collected from Antalya-Türkiye, were determined as in vitro and in silico. GC-MS analysis of the hexane extract revealed a high content of fatty acids, with hexadecanoic acid constituting half of the total fatty acid content. LC-HRMS analysis of the DCM:MeOH extract identified ascorbic acid as the most abundant compound, followed by (-)-epigallocatechin and salicylic acid. The DCM:MeOH extract exhibited potent cytotoxicity against MDA-MB-231 and MCF7 breast cancer cell lines, outperforming doxorubicin with lower IC50 values and a higher selectivity index. Additionally, the extract demonstrated significant antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans, along with selective inhibition of acetylcholinesterase (hAChE) over butyrylcholinesterase (hBChE). Molecular docking and dynamics studies revealed that apigenin-7-O-glucoside and epigallocatechin form stable interactions with estrogen receptor alpha (ERα) and hAChE, suggesting their potential as inhibitors. In silico ADME studies indicated favorable pharmacokinetic profiles for the detected compounds, supporting their potential as drug candidates. The promising cytotoxic activity of the P. capitatus extracts, coupled with significant antimicrobial properties and selective hAChE inhibition, highlights their therapeutic potential for breast cancer treatment, infection management, and neurodegenerative disease intervention.

Ionic conduction and cathodic properties of CaMO3 (M=Fe and Mn) electrode materials via molecular dynamics and first-principles simulations

Calcium-ion(Ca-ion) batteries are gaining ever-increasing attention for next-generation energy storage systems due to affordability, highly abundant, high energy density, high theoretical capacity, and low redox potential close to Li-ion. In this work, we deployed the first-principles and classical molecular dynamics simulations to investigate the electronic and diffusive properties of isostructural ternary perovskite CaMO3 (M= Fe and Mn). The transport properties at various temperatures from ion dynamics and electronic properties of CaMO3 perovskites are examined using classical molecular dynamics and quantum mechanical simulations, respectively. We present the microscopic origin of the diffusion of multivalent ions like Ca2+ within the crystal structure of perovskite material and the effects of two transition metals, manganese and iron. Dynamic studies of Ca-ions were performed using molecular dynamic simulation, which depicts the diffusivity and conductivity of Ca-ion in CaMO3 material. We find that the diffusivity in both the crystals increases with temperature; as a result, conductivity increases. Among both the crystals, CaFeO3 requires less activation energy for diffusion and ionic conduction than CaMnO3. Using density functional theory, we calculated specific capacity, electronic density of states, phase stability and equilibrium cell voltage, and charge transfer process during intercalation-deintercalation from first-principles calculations. The electronic behavior of these materials shows that CaFeO3 has better electronic and transport properties than CaMnO3.

Multiple nanodroplets coalescence in the coupling of electric field and swirl centrifugal field: A molecular dynamics study

Multiple nanodroplets coalescence in the coupling of electric field and swirl centrifugal field: A molecular dynamics study

Phytochemistry, antioxidant and anti-diabetic activities of Sterculia villosa in-vitro

ObjectiveAs ongoing research continues, many antidiabetic agents still have many side effects which is the reason why more and more people resort to traditional medicines such as Traditional Chinese Medicine (TCM). There are many Therapeutic Species of Sterculia spp. that are commonly used in TCM practices. Here, we have studied one of such TCM herbal plants, namely Sterculia villosa Roxb. (Chinese: 绒毛苹婆), for its antidiabetic potential. In this way, the study intends to assess its effectiveness and examine its suitability as a raw natural medicine for diabetes management in traditional medicine. MethodIn-vitro anti-diabetic property was evaluated by α-amylase and α-glucosidase enzyme inhibition and glucose uptake assays. Metabolomic profiling by GC-MS was conducted to determine the probable phyto-constituents in S. villosa. These phyto-compounds were further subjected to in-silico molecular docking studies, identifying stigmasterol as the most potent anti-diabetic phyto-compound. Glucose uptake efficacy was estimated by a fluorescence microplate reader employing glucose analog 2-NBDG. Molecular dynamic studies (MDS) were carried out with GROMACS to comprehend the protein-ligand binding stability. ResultsStigmasterol showed enhanced enzyme inhibition for both α-amylase (IC50 23.84±1.37 μM) and α-glucosidase (IC50 39.56±1.5 μM). Line-weaver Burk plot revealed competitive and mixed modes of inhibition for α-amylase and α-glucosidase, respectively. The GC-MS analysis identified 23 vital phyto-compounds present in the methanolic extract of the S. villosa leaves. Upon screening against crucial anti-diabetic proteins by in-silico molecular docking, stigmasterol followed by lupeol, Stigmasta-3,5-diene, and γ-sitosterol were found to be the most effective lead compounds. Stigmasterol also showed potent hypoglycaemic efficacy, as evidenced by augmentation of 2-NBDG glucose uptake in 3T3-L1 cells. The docking and simulation studies against four crucial anti-diabetic targets, α-amylase, α-glucosidase, GLUT 4, and IRS-1, predicted that stigmasterol exhibits a multi-pronged anti-diabetic activity mediated by α-amylase inhibition and activation of IRS1 pathway, simultaneously. The MDS studies highlighted that stigmasterol showed stable interactions with these four proteins, as evidenced by the RMSD, RMSF and hydrogen bond analysis. ConclusionThe results of this study are intriguing, as they identify stigmasterol, sourced from the medicinal plant S. villosa, as a potential breakthrough in the field of diabetic remediation. This discovery paves the way for further research and development of stigmasterol as a more effective and safer treatment for diabetes.

Molecular dynamics study of mechanical stability of Ti4C3 MXene subjected to chirality, temperature, strain rate, and point-vacancy for Lithium-ion batteries

Two-dimensional Ti4C3 MXene has recently emerged as a promising electrode for Lithium-ion batteries (LIBs) because of its outstanding ion-transport abilities and high Li-absorbability. This study employed molecular dynamics simulation to explore the mechanical stability of Ti4C3 MXene subjected to various temperatures, strain rates, and vacancy concentrations. A slightly superior tensile strength and elasticity modulus have been observed along zigzag directions, measuring 148.14 GPa and 29.17 GPa, respectively. On the other hand, armchair-oriented Ti4C3 MXene shows a considerably greater fracture strain of 0.259 due to its strain-hardening tendency at lower temperatures. Elevated temperature decreases both fracture strength and fracture strain, which is opposite to the effect of strain rate. Armchair loading has been revealed to be more sensitive to strain rate than its counter direction. Unlike temperature and strain rate, point vacancy significantly deteriorates the elastic modulus of Ti4C3 MXene. Carbon vacancies are more probable than titanium vacancies, which have less formation energy. The atomistic deformation profile supports the predicted values of fracture strain from stress-strain behavior. This in-depth study offers a detailed understanding of the mechanical behavior of Ti4C3 MXene under diverse circumstances, which will aid further experimental study and be beneficial for adopting Ti4C3 as anode materials in LIBs.

Transient microstructural behavior of methanol/n-heptane droplets under supercritical conditions

Supercritical fluids exist widely in nature and have enduringly attracted scientific and industrial interest. In power systems like liquid rocket engines, fluids undergo the trans-critical process transferred from the subcritical state to the supercritical state, and the phase change process exhibits different features distinguished from subcritical evaporation. In this work, we conducted a series of molecular dynamics studies on the behavior of methanol (MeOH), n-heptane (C7), and binary C7/MeOH droplets under supercritical nitrogen environments. The emphasis is on clarifying the transient characteristics and physical origins of the trans-critical evolution of droplets. During the trans-critical process, droplets are found to experience an unstable period without a spherical shape, where the droplet diameter no longer decreases, violating the traditional d2-law rule. The occurrence of nonspherical droplets is related to the microstructural behavior of trans-critical droplets. Two types of microscopic structures within the droplet are identified: large-scale thermally induced clusters for long-chain C7 and hydrogen-bond connected network-like structures for MeOH, which contains hydroxyl (–OH) groups. Based on these findings, the mechanism behind the evolution of trans-critical droplets is illustrated. Finally, we determine the boundary of ambient conditions in the form of dimensionless expressions Tr−1=a(pr−1)−b, which dictate whether droplets can maintain a spherical shape during the trans-critical process.

Synthesis, biological evaluation, docking and molecular dynamics studies of Biginelli-type tetrahydropyrimidine analogues: Antimicrobial, cytotoxicity and antioxidant activity

Tetrahydropyrimidines have a fascinating scaffold that has garnered substantial attention from pharmacists and medicinal chemists. They are heterocyclic compounds used in anti-cancer, anti-microbial, and antioxidants therapies. Herein, a group of tetrahydropyrimidines were provided by using urea, α-ketoacid/β-ketoester, and appropriate aromatic aldehydes. Then, the antioxidant properties of the derivatives were investigated by the DPPH assay. Besides, the cytotoxicity activity of derivatives was evaluated on two MCF-7 and HepG-2 cell lines. The anti-microbial activity of derivatives was also assessed on two positive gram strains, two negative gram strains, and a fungal strain. Derivatives 4a and 4e showed the strongest antioxidant properties, with IC50s of 0.83 and 0.07 mg/mL, respectively. Compounds 4a and 4d were the most potent compounds, with IC50s of 15.81 and 12.34 µM, respectively, on both cancer cell lines. Furthermore, compounds 4b, 4j, and 4i showed the highest anti-microbial activity on S. aureus (MIC = 7.31 µM), B. subtilis (MIC = 10.81 µM), and E. coli (MIC = 11.45 µM), P. aeruginosa (MIC = 8.12 µM), and C. albicans (MIC = 12.03 µM), respectively. Then, the oral bioavailability and pharmacokinetic properties of compounds were predicted. Moreover, the most possible sites of the molecules that are metabolized by the main cytochromes were estimated. Then, the in silico cardiotoxicity and Cyto-safe properties of the compounds were studied. Finally, to determine the stability of the analogues in the Eg5 active site, docking and molecular dynamics simulations were performed.

A GIS and Remote Sensing-based Approach on Supraglacial Lake Dynamics Study in the Himalayan Glaciers

ABSTRACT The formation of supraglacial lakes is one of such essential indications for the ice mass loss as well as global warming in the glaciers of the high mountains. Here, a total of 2072 glaciers with size >2km2 and supraglacial debris cover >15% were taken for the supraglacial morphodynamic study in the Himalaya. Moreover, a detailed study was performed in Everest and Uttrakhand regions as representative of eastern and western Himalaya concerning the supraglacial lake's behavior and its future consequences. Normalized elevation, feature selection techniques, cumulative frequency, and lake density were adopted for the supraglacial lake morphodynamics analysis. Lake size and lake numbers were continuously increasing since 1990 in those two sub-regions as well as in the whole Himalaya. A total of 14421, 23215, 24263 and 26112 supraglacial lakes and 58.55km2, 72.75km2, 73.34km2 and 87.75km2 of supraglacial lake size were demarcated for the years 1995, 2010, 2015 and 2019, respectively in the Himalaya. Unlike Uttarakhand and Arunachal regions, supraglacial lake density is higher in Everest, Sikkim and Bhutan regions. Most of the supraglacial lakes were gathered at the lower part of the ablation area (NE<2). Overall lake size is higher in Everest region (8.9km2) than in the Uttarakhand region (3.2km2). Similarly, Lake coalescing was also observed in Everest region only. The feature selection technique exhibited that the lake density is controlled mostly by slope followed by ice thickness and surface velocity.

A tribo-dynamics model of ball screws based on flexible body element

Dynamic actuation accuracy of ball screws is dramatically affected by screw flexible deformation and the behaviors of ball-groove interface such as friction, stiffness and damping. However, few dynamics studies have considered the screw flexible deformation and rubbing interface behaviors in ball screws. In this study, a dynamics model is developed by including both the screw flexible deformation and lubrication interface behavior. Discretization of the screw/nut is completed using the 6 degree-of-freedom Timoshenko beam element. The tribological properties of ball-groove interface are solved by the mixed lubrication model. Comparison with experimentally tested nut acceleration frequencies verifies the correctness of theoretical model. On this basis, the effects of nut motion, nut position and rough surface on the dynamic response are analyzed. With the increase of time, the screw axial displacement decreases with a certain slope and is accompanied by periodic vibrations. The centers of axis trajectories at different nut positions are far apart. From Hertz, smooth surface to rough surface, the interface stiffness coefficient decreases and the nut vibration amplitude grows. The novel tribo-dynamics model can provide a theoretical basis for fault diagnosis and performance optimization of ball screws.

Внутригодовая динамика химического состава воды в устье реки Баксан

The article presents the results of a study of the intra-annual dynamics of the chemical composition of water at the mouth of the Baksan River in 2023. The intra-annual dynamics of transparency, pH, mineralization, hardness, permanganate oxidizability, content of macrocomponents (bicarbonates, chlorides, sulfates, nitrites, nitrates) and iron compounds were studied. According to average annual values, the water of the studied object has average hardness and belongs to the hydrocarbonate, fresh waters of rivers of average mineralization. An excess of the maximum permissible concentration for sulfates, nitrates and iron compounds was detected. It is shown that the hydrochemical regime of the studied water body is interconnected with level and thermal regimes and is influenced by anthropogenic factors. The data obtained are necessary to identify patterns of distribution of substances in natural geosystems located in the Malka River basin, of which the Baksan River is a first-order tributary.

Engineering consensus in static networks with unknown disruptors

Distributed control can increase system scalability, flexibility, and redundancy. Foundational to such scalability via decentralisation is consensus formation, by which decision-making and coordination are achieved. However, decentralised multi-agent systems are inherently vulnerable to disruption. To develop a resilient consensus approach, inspiration is taken from the study of social dynamics; specifically, the Deffuant Model which evaluates the impact of tolerance in social systems. A dynamic protocol is presented enabling efficient consensus to be reached with an unknown number of disruptors present within a multi-agent system. By inverting typical social tolerance, agents filter out extremist non-standard opinions that would drive them away from consensus. This approach allows distributed systems to deal with unknown disruptions, without knowledge of the network topology or the numbers and behaviours of the disruptors, a general requirement of other resilient consensus algorithms. A disruptor-agnostic algorithm is particularly suitable to real-world applications where information regarding disruptors or network properties is typically unknown. Faster, tighter, and more robust convergence can be achieved across a range of scenarios with the social dynamics inspired algorithm presented herein, when compared with Mean-Subsequence-Reduced-type methods.

Identification of steroidal cardenolides from Calotropis procera as novel HIV-1 PR inhibitors: A molecular docking & molecular dynamics simulation study.

Background & objectives Despite advancements in antiretroviral therapy, drug-resistant strains of HIV (human immunodeficiency virus) remain a global health concern. Natural compounds from medicinal plants offer a promising avenue for developing new HIV-1 PR (protease) inhibitors. This study aimed to explore the potential of compounds derived from Calotropis procera, a medicinal plant, as inhibitors of HIV-1 PR. Methods This in silico study utilized natural compound information and the crystal structure of HIV-1 PR. Molecular docking of 17 steroidal cardenolides from Calotropis procera against HIV-1 PR was performed using AutoDock 4.2 to identify compounds with higher antiviral potential. A dynamic simulation study was performed to provide insights into the stability, binding dynamics, and potential efficacy of the top potential antiviral compound as an HIV-1 therapeutic. Results We found that all tested cardenolides had higher binding affinities than Amprenavir, indicating their potential as potent HIV-1 PR inhibitors. Voruscharin and uscharidin displayed the strongest interactions, forming hydrogen bonds and hydrophobic interactions with HIV-1 PR. Voruscharin showed improved stability with lower RMSD (Root Mean Square Deviation) values and reduced fluctuations in binding site residues but increased flexibility in certain regions. The radius of gyration analysis confirmed a stable binding pose between HIV-1 PR and Voruscharin. Interpretation & conclusions These findings suggest that Calotropis procera could potentially be a source of compounds for developing novel HIV-1 PR inhibitors, contributing to the efforts to combat HIV. Further studies and clinical trials are needed to evaluate the safety and efficacy of these compounds as potential drug candidates for the treatment of HIV-1 infection.

Molecular dynamic simulation study on effect of anionic–nonionic surfactants on decane desorption from SiO2 surface

During oil production, some amount of crude oil is adsorbed on the rock layer. Therefore, surfactants are needed to detach the residual crude oil from this layer, thereby improving the overall oil recovery rate. In this study, five kinds of anionic–nonionic surfactants were designed by changing the length of ethylene oxide (EO) chains based on the structure of saturated cardanol. 8PO8EOSO3 exhibited good oil-detachment effectiveness, and this was assessed by studying the energy of interface interaction between the solid phase (SiO2) and the liquid phase (oil phase molecules, surfactants, and water). The density distribution data further elucidated that the good interface properties of 8PO8EOSO3 affected the degree of aggregation of the oil phase molecules on the SiO2 surface. This was mainly because the appropriate length of EO chains could realize optimal diffusion coefficients at the oil–water interface. Thus, in the 8PO8EOSO3 system, the oil phase molecules exhibited greater intermolecular distance and weak interactions with SiO2 (radial distribution function). Further, the study of the solid–liquid interface properties and effect of different chain lengths of EO chains on desorption showed that the appropriate number of and EO chains was an important factor in designing the structure of the extended surfactant to ensure that the surfactant realizes a high degree of detachment of the oil phase from SiO2.

Molecular Dynamics Study of the Formation of Porous Films by Room-Temperature Physical Vapor Deposition of Silica

Molecular Dynamics Study of the Formation of Porous Films by Room-Temperature Physical Vapor Deposition of Silica

Investigating the nano-bubbles aggregation in two-phase systems: A molecular dynamics study

These days, understanding the nano-bubble aggregation has attracted lot of attentions in various fields from medicine to industries. In the present work, by means of molecular dynamics simulation, effects of surface conditions on nano-bubbles aggregation in two-phase systems have been studied. Hence, in the argon two-phase system, two heat sources have been installed on a Pt substrate and their distance has been changed: From the first to seventh system, the gap between these two surface-mounted heat sources is 46.80, 39.90, 31.20, 24.30, 23.40, 11.70, and 00.00 Å, respectively. Corresponding to the simulation results, the effect of the number of heat sources and their distances on the individual-bubbles growth rate is quite evident: whatever the spacing between two adjacent heats are smaller, the formed nano-bubbles are more stable or larger as well, and have longer lifespan.Besides, according to the calculation of the changes in quantities of the bubble contact angle (CA/deg.), size (H/Å), diameter of the cross-section area (L/Å), and thickness of the outer layer (A/Å), it was observed that each of these nano-bubbles, which have the same formation conditions and exist simultaneously in the equilibrium system, behave differently.Interestingly, by reducing the distance between the two sources in the range of 31.20–11.70 Å, owing to the existence of a film layer of vapor molecules between two neighboring nano-bubbles, the bubbles aggregation phenomena occur. At last, if the gap between the heat two sources becomes zero, an ultra-stable nano-bubble, which will has the largest size, lifetime and stability, is observed.

Molecular Dynamics Study on the Storage of Carbon Dioxide in Single-Walled Carbon Nanotubes at Low Pressures.

The storage of carbon dioxide (CO2) in single-walled carbon nanotubes was studied with molecular dynamics simulation. The influences of the temperature, system average density, and nanotube size on the CO2 pressure, density distribution, and intermolecular forces were investigated. Multilayer adsorption inside nanotubes was observed as average density increases at lower pressures, which is desirable in industry. Meanwhile, a nanobubble was gradually formed in the center of the nanotube, and the system with the nanobubble was stabilized by the balance between the positive Laplace pressure and the negative liquid pressure when the size of the nanobubble was higher than the critical size. The adsorption effect of the nanotube wall leads to high local condensed density near the wall and stronger intermolecular repulsion, while Laplace pressure results in a low local condensed density in the adsorbed CO2 near the bubble interface and stronger intermolecular attraction. The stretching effect that originates from the intermolecular force dominated by attraction in the condensed phase leads to low pressure. At the critical nanobubble size, a higher CO2 average density can be achieved by lowering the temperature and increasing the nanotube radius or length. When the adsorption impact of the nanotube wall on bubble destabilization becomes negligible as the adsorption layer thickens, further increasing the nanotube radius leads to limited increase of the average density at the critical nanobubble size. The simulation of a graphene-sealed nanotube confirmed the formation of a vapor nanobubble under more realistic conditions. This work provides insights into utilizing carbon nanotubes as a material for CO2 capture with multilayer adsorption at lower pressures.

Exploring multitarget potential of Piper nigrum fruit constituents for Alzheimer's disease: An AI-driven strategy

BackgroundAlzheimer's disease (AD) is a neurodegenerative disease that leads to development of cognition and memory dysfunctions. Currently, there is no known cure for AD, although limited medications are approved for the management of disease condition. Various plant-based leads give new hope for considering phytoconstituents as anti-AD drugs. The Piper nigrum L. fruit extract was reported to have anti-Alzheimer's activity. It creates an interest in the finding of active moieties that may be accountable for anti-AD activity. Hypothesis/PurposeIdentification of multitarget directed ligands isolated from Piper nigrum fruits through AI based studies. Study designThe phytochemical analysis of alkaloid fraction was carried out by LCMS, followed by the evaluation of constituents through in silico studies. MethodsThe fruits methanolic extract was prepared by cold maceration technique. The chemical profiling of the alkaloidal fraction was carried out using LCMS/MS analysis. The obtained compound's target hit genes were identified through network pharmacology studies using String, Metascape, and Cytoscape tools. Further, docking studies and MD simulations were carried out using AutoDock4 and Desmond-Maestro software. Then, electrochemical properties of hit compound P4 were determined using Gaussview6 software. ResultsFrom LCMS/MS analysis data, 29 compounds were considered based on compound intensity and accuracy (>95 %). Then, 41 common gene targets were identified from AD genes and compound-targeted genes. The 41 common genes in the PPI network suggested that AChE and BACE1 were the most abundant proteins. Further, docking studies revealed the hit compound P4 binding interaction and energies when compared to other 28 ligands. The molecular dynamics studies showed that P4-AChE and P4-BACE1 complexes were stable, and there were no RMSD and RMSF fluctuations were observed up to 100 ns. Further, PCA and MM-GBSA analysis data supported that complexes (P4-AChE and P4-BACE1) were stable. The DFT and surface properties indicated that compound P4 was ideal candidate for AD treatment and must be considered for further biological activity studies. ConclusionThe study identified compound P4 (dehydropipernonaline) from alkaloidal fraction of Piper nigrum fruits, suggesting it may be hit candidate for AD treatment.

Insight into HTPB pyrolysis mechanism under high-temperature: A reactive molecular dynamics study

Hydroxyl-terminated polybutadiene (HTPB) is widely utilized in solid and hybrid rocket propellants due to its mechanical properties and combustion performance. Insight into its pyrolysis process is key to enhancing combustion efficiency in rocket engines. This study employs ReaxFF molecular dynamics (MD) simulations to explore the pyrolysis mechanism of HTPB under extreme conditions, with temperatures ranging from 1000 K to 2000 K. The results identify the primary degradation products and elucidate their formation mechanisms. The simulation reveals that C-C bond cleavage at polymerization sites is the initial step, followed by the formation of linear oligomers and butadiene. Subsequent reactions, including hydrogenation and dehydrogenation, lead to the generation of smaller molecular species. The kinetic analysis confirms that HTPB pyrolysis follows first-order reaction kinetics, with an activation energy of 8.12 kcal/mol. The findings are compared with existing experimental data, highlighting the influence of thermal environments on pyrolysis mechanisms and product distributions.