Molecular Dynamics Simulations Research Articles

Structure-guided drug repurposing identifies aristospan as a potential inhibitor of β-lactamase: insights from virtual screening and molecular dynamics simulations

The rise of β-Lactamase mediated antibiotic resistance is a major concern for public health; hence, there is an urgent need to find new treatment approaches. Structure-guided drug repurposing offers a promising approach to swiftly deliver essential therapeutics in the fight against escalating antibiotic resistance. Here, a structure-guided virtual screening approach was used involving drug profiling, molecular docking, and molecular dynamics (MD) simulation to identify existing drugs against β-Lactamase-associated drug resistance. We exploited a large panel of FDA-approved drugs to an extensive in silico analysis to ascertain their ability to inhibit β-Lactamase. First, molecular docking investigations were performed to assess the binding affinities and interactions of screened molecules with the active site of β-Lactamase enzymes. Out of all the screened candidates, Aristospan was identified to possess promising characteristics, which include appropriate drug profiles, high binding specificity, and efficiency towards the binding pocket of β-Lactamase. Further analysis showed that Aristospan possesses several desirable biological characteristics and tends to bind to the β-Lactamase binding site. To explore the interactions further, the best docking pose of Aristospan was selected for MD simulations to assess the thermodynamic stability of the drug-enzyme complex and its conformational changes over 500 ns. The MD simulations in independent replica runs demonstrated that the β-Lactamase-Aristospan complex was stable in the 500 ns trajectory. These enlightening results suggest that Aristospan may harbor the potential for further evolution into a possible β-Lactamase inhibitor, with potential applications in overcoming antibiotic resistance in both Gram-positive and Gram-negative bacteria.

Orientational Disorder of Alcohol Molecules at Their Solution Surfaces in Low Concentration Range: A Molecular Dynamics Simulation Study.

Molecular dynamics (MD) simulations of short-chain alcohols (methanol, ethanol, and 1-propanol) in solution were carried out to examine the orientational disordering (randomizing) of alcohol molecules at the surface under diluted conditions. Recent vibrational sum frequency generation (VSFG) spectroscopy, combined with photoelectron spectroscopy, has successfully measured the disordering structure at low concentrations. The present MD simulations accurately reproduce this observation for the first time. To ensure reliable results through MD simulations, several widely used force field models for water and alcohol, including polarizable models, were examined. This examination involved a comparison of structural and thermodynamic quantities, such as surface density times orientation and surface excess concentration, which were obtained through surface-specific measurements like VSFG spectroscopy and surface tension measurements. It is found that the width of the density profile for alcohol molecules at the surface, along the surface normal, increases as the concentration decreases in the diluted condition, which is consistent with the results obtained from the previous neutron and X-ray grazing incidence reflection experiments. A molecular mechanism explaining the disordering of alcohol molecules with decreasing concentration is also discussed.

Molecular docking and molecular dynamics of hypoxia-inducible factor (HIF-1alpha): towards potential inhibitors

HIF-1α is a primary regulator in the adaptation of cancer cells to hypoxia. The aim was to find out new inhibitors of the HIF-1α. A molecular dynamic (MD) simulation performed on HIF-1α showed stable dynamic features. Virtual screening of 217 anticancer drugs was performed along with a positive control (2-Methoxyestradiolm, 2-ME2) on an optimized HIF-1α and dynamically simulated structure. Docking results produced two compounds namely pycnidione and nilotinib of high binding affinity −9.34 kcal/mol and −9.04 kcal/mol respectively, whereas 2-ME2 displayed a relatively lower affinity (-6.68 kcal/mol). For the three complexes, MD of 200 ns simulation was run. Data analysis showed that the three medications behaved similarly in the MD simulation. Nilotinib had a lower RMSD and higher SASA than the other complexes. In addition, the Nilotinib-HIF-1α combination had a lower RMSF value, a flatter Rg, and a number of hydrogen bonds similar to other complexes. MM-GBSA analysis revealed that nilotinib, pycnidione and 2-ME2 compounds had free binding energy of −23.77 ± 5.29, −21.85 ± 4.24 and −7.53 ± 6.62 kcal/mol respectively. Nilotinib and pycnidione bind competitively to HIF-1α, with nilotinib showing consistent molecular-dynamic properties. They relatively pass the blood-brain barrier, non-carcinogenic, and have IV-category acute oral toxicity. They have low CYP inhibitory characteristics. Further investigations are therefore warranted to elucidate their implications in hypoxia pathways, cell proliferation, apoptosis, survival, and metastatic potential.

A study on the thermal behavior of coal gangue mountains under airflow influence based on MD and CFD simulations

The long-term accumulation of coal gangue can lead to an increase in internal temperature. If the temperature becomes excessive, it can cause spontaneous combustion, posing serious environmental risks. The process is significantly influenced by external airflow. This study analyzes the thermodynamic properties and oxidation heat release rate of coal gangue samples through laboratory experiments. Subsequently, molecular dynamics (MD) simulations are used to investigate the mechanism of oxidation heat release during the heating process of coal gangue under varying oxygen supply conditions. Based on these findings, a coupled three-field model for the heating process of coal gangue mountains is developed. Using computational fluid dynamics (CFD) methods, transient simulations are conducted to analyze the internal thermal behavior of coal gangue mountains under the influence of external airflow, clarifying the risks of spontaneous combustion. The results indicate that after reaching T2 (295.16 °C), coal gangue enters an accelerated oxidation phase, with an increased heat release rate, heightening the risk of spontaneous combustion. The oxidation heat release rate of coal gangue accelerates with rising temperature and oxygen concentration, entering a rapid reaction phase after 300 °C, with a sharp increase in reaction rate. Compared to N2, coal gangue surfaces exhibit stronger adsorption of O2, and temperature changes affect N2 diffusion more sensitively (O2 diffusion coefficient increases by 0.312 Å2/ps, N2 diffusion coefficient increases by 0.334 Å2/ps). The isosteric heat of O2 adsorption in coal gangue decreases significantly with increasing adsorption amount, and higher temperatures hinder competitive adsorption of O2. The temperature in the deep and foot areas of the coal gangue mountains is lower, while the middle and upper areas near the slope surface exhibit higher temperatures, indicating a higher risk of spontaneous combustion in these regions. When environmental wind speed is too high or too low, both the internal temperature of the coal gangue mountains and the area of spontaneous combustion risk zones decrease. At a wind speed of 3 m/s, the spontaneous combustion risk zone reaches its maximum area of 73.47 m2, but when the wind speed increases to 7 m/s, the risk area decreases to 65.72 m2.

Nanomaterials and methods for cancer therapy: 2D materials, biomolecules, and molecular dynamics simulations.

This review explores the potential of biomolecule-based nanomaterials, i.e., protein, peptide, nucleic acid, and polysaccharide-based nanomaterials, in cancer nanomedicine. It highlights the wide range of design possibilities for creating multifunctional nanomedicines using these biomolecule-based nanomaterials. This review also analyzes the primary obstacles in cancer nanomedicine that can be resolved through the usage of nanomaterials based on biomolecules. It also examines the unique in vivo characteristics, programmability, and biological functionalities of these biomolecule-based nanomaterials. This summary outlines the most recent advancements in the development of two-dimensional semiconductor-based nanomaterials for cancer theranostic purposes. It focuses on the latest developments in molecular simulations and modelling to provide a clear understanding of important uses, techniques, and concepts of nanomaterials in drug delivery and synthesis processes. Finally, the review addresses the challenges in molecular simulations, and generating, analyzing, and developing biomolecule-based and two-dimensional semiconductor-based nanomaterials, and highlights the barriers that must be overcome to facilitate their application in clinical settings.

Achieving Sub-ppm Sensitivity in SO2 Detection with a Chemically Stable Covalent Organic Framework.

We report the inaugural experimental investigation of covalent organic frameworks (COFs) to address the formidable challenge of SO2 detection. Specifically, an imine-functionalized COF (SonoCOF-9) demonstrated a modest and reversible SO2 sorption of 3.5 mmol g-1 at 1 bar and 298 K. At 0.1 bar (and 298 K), the total SO2 uptake reached 0.91 mmol g-1 with excellent reversibility for at least 50 adsorption-desorption cycles. An isosteric enthalpy of adsorption (ΔHads) for SO2 equaled -42.3 kJ mol-1, indicating a relatively strong interaction of SO2 molecules with the COF material. Also, molecular dynamics simulations and Møller-Plesset perturbation theory calculations showed the interaction of SO2 with π density of the rings and lone pairs of the N atoms of SonoCOF-9. The combination of experimental data and theoretical calculations corroborated the potential use of this COF for the selective detection and sensing of SO2 at the sub-ppm level (0.0064 ppm of SO2).

A Comprehensive Journey of a Vanillic Aldehyde-Chloroaniline Schiff Base from Solvent-Free Synthesis to Electronic Structure, In Silico and In Vitro Biological Analysis

Schiff bases possess a range of unique physical, chemical and medicinal properties, which contribute to their potency as biological agents. A Schiff base was synthesized, which consisted of 4-chloro aniline and vanillin. The successful formation of the compound was confirmed by their comparable FTIR, UV–Vis, 1HNMR and [Formula: see text]CNMR spectra. The compound was analyzed using X-ray crystallography, which revealed that it crystallizes in the monoclinic system with the space group P21/c. The Hirshfeld surface analysis revealed valuable information about the intermolecular interactions present in the crystal lattice. The most common contacts observed were between hydrogen and hydrogen, as well as carbon and hydrogen. The obtained fluorescence values of 375 nm and 412 nm at excitation wavelength 322 nm strongly indicated the luminescent nature of the compound. The thermal stability of the compound was assessed through thermogravimetric analysis (TGA). DFT was used to optimize the geometry using the B3LYP/cc-pVDZ basis set. The compound exhibited an energy gap of 2.35 electron volts (eV). According to the analysis of molecular electrostatic potential, C and O atoms were found to be electrophilic. According to Mulliken charge analysis, C atoms possess both positive and negative charges, hydrogen atoms exclusively carry positive charges, and Cl, O and N atoms exclusively carry negative charges. Upon analysis of the molecule, the electron localization function discovered that the atoms of carbon, nitrogen and chlorine exhibited delocalized electron density. Also, the localized orbital locator identified the localized orbital positions in the hydrogen atoms. The reduced density gradient (RDG) maps exhibit a wide range of noncovalent interactions. In comparison to the standard amoxicillin, the synthesized compound demonstrated moderate antimicrobial efficacy against the gram-positive bacteria Klebsiella pneumoniae and the fungi Candida albicans. The compound’s concentration-dependent antioxidant and anti-inflammatory properties were demonstrated through in vitro biological evaluation using 2,2-diphenyl-1-picrylhydrazyl and human red blood cell (HRBC) methods. The compound was docked using the proteins 7BYE and 4LEB were chosen from both organisms. The lowest binding attractions obtained were -3.40 kcal/mol for 7BYE and -4.51 kcal/mol for 4LEB. To investigate the stability of the protein–ligand complex, molecular dynamic simulation was employed. The ligands in silico toxicity potentialities were analyzed using seven toxicity models and the results indicated that the ligand is biocompatible.

Utilizing metal-organic framework porosity for efficient antibiotic separation and sustained release

Metal-organic frameworks (MOFs) have emerged as a revolutionary class of nanoporous materials due to their highly tunable porosity and functionality. With the vast number of MOFs being discovered, traditional experimental techniques to identify the best candidates for various applications, including water treatment and drug delivery become time-consuming and expensive. This is where computational screening offers a powerful solution. We present a computational screening strategy using Monte Carlo (MC) simulation to identify the promising MOFs among over 14,000 MOFs for efficient absorption, membrane separation, and sustained delivery of antibiotics (e.g., azithromycin, AZ). The MC simulation was used to calculate the loading capacity and isosteric heat of the AZ absorption. These absorption properties were correlated with several structural characteristics of the MOF, including the largest cavity diameter, pore limiting diameter, accessible volume, helium void fraction, etc. Critical evaluation of the correlation results identified the best MOFs for AZ absorption, separation, and delivery. The results recommended a total of 578 MOFs, with 126 identified as suitable for use as AZ adsorbents or drug carriers, and 452 for use as membranes to separate AZ from water. Furthermore, the adsorption mechanism of the top MOF was analyzed using molecular dynamics simulation and non-covalent interactions. The solvation-free energy of AZ was evaluated in various solvents to identify the most effective solvent for extracting AZ from MOFs, thereby facilitating the regeneration of the MOF.

Achieving Sub‐ppm Sensitivity in SO2 Detection with a Chemically Stable Covalent Organic Framework

AbstractWe report the inaugural experimental investigation of covalent organic frameworks (COFs) to address the formidable challenge of SO2 detection. Specifically, an imine‐functionalized COF (SonoCOF‐9) demonstrated a modest and reversible SO2 sorption of 3.5 mmol g−1 at 1 bar and 298 K. At 0.1 bar (and 298 K), the total SO2 uptake reached 0.91 mmol g−1 with excellent reversibility for at least 50 adsorption‐desorption cycles. An isosteric enthalpy of adsorption (ΔHads) for SO2 equaled −42.3 kJ mol−1, indicating a relatively strong interaction of SO2 molecules with the COF material. Also, molecular dynamics simulations and Møller–Plesset perturbation theory calculations showed the interaction of SO2 with π density of the rings and lone pairs of the N atoms of SonoCOF‐9. The combination of experimental data and theoretical calculations corroborated the potential use of this COF for the selective detection and sensing of SO2 at the sub‐ppm level (0.0064 ppm of SO2).

Probing the friction mechanism of diamond-like carbon films in aqueous environments based on molecular dynamics simulations

Abstract The frictional behavior of diamond-like carbon (DLC) films in an aqueous environment is of tremendous interest. To compare the impacts of the quantity of water molecules, sliding velocity, and loading on the friction behavior of DLC films, a molecular model of DLC films in an aqueous environment was built. The results show that the DLC film under high load and high sliding velocity leads to severe friction behavior, but the water molecules can prevent the occurrence of this severe friction behavior. Also increasing the number of water molecules can effectively reduce the increase in friction during the running-in stage and keep it at a low value. The primary explanation is that if there are enough water molecules, they will create a stable water film at the friction interface and prevent large-scale contact and distortion between the upper and lower DLC films, significantly reducing friction.

Formation mechanism of soot in pyrolysis of 2-methylfuran under high temperature based on ReaxFF molecular dynamics simulation

In this study, the detailed mechanism of soot formation under high temperature pyrolysis of 2-methylfuran (2-MF) has been investigated by using Reactive force field molecular dynamics (ReaxFF MD) simulation. The MD analysis shows that 2-MF undergoes ring cleavage and the removal of CO/HCO/CH2CO/CH3CO, which results in the production of the C2-C4 species, promoting the formation of the initial ring molecules. The clustering of hydrocarbons by radical-chain reaction (CHRCR) mechanism plays a significant role in the mass growth of both polycyclic aromatic hydrocarbons (PAHs) and initial soot particles. The main contributors to this process are C2H2 and resonance-stabilized free radicals of C3 and C4. The H-abstraction-C2H2-addition (HACA) mechanism is important for the formation of surface active sites for PAHs and initial soot to some extent. In addition, the soot formation capacity of 2,5-dimethylfuran (25DMF) and 2-MF are compared. Under the same simulation conditions, 25DMF exhibits a higher capacity to form soot. Compared with 2-MF, 25DMF pyrolysis forms more ring-containing species at the initial stage, particularly cyclopentadiene and its derivatives. These compounds have the ability to promote the formation of PAHs, thus providing further support to the experimental-based theory.

A Rationally Designed Azobenzene Photoswitch for DNA G‐Quadruplex Regulation in Live Cells

AbstractG‐quadruplex (G4) DNA structures are increasingly acknowledged as promising targets in cancer research, and the development of G4‐specific stabilizing compounds may lay a fundamental foundation in precision medicine for cancer treatment. Here, we propose a light‐responsive G4‐binder for precise modulation of drug activation, providing dynamic and spatiotemporal control over G4‐associated biological processes contributing to cancer cell death. We developed a specialized fluorinated azobenzene (AB) switch equipped with a quinoline unit and a positively charged carboxamide side chain, Q‐Azo4F‐C, designed for targeted binding to G4 structures within cells. Biophysical studies, combined with molecular dynamics simulations, provide insights into the unique coordination modes of the photoswitchable ligand in its trans and cis configurations when interacting with G4s. The observed variations in complexation processes between the two isomeric states in different cancer cell lines manifest in more than 25‐fold reversible cytotoxic activity. Immunostaining conducted with the structure‐specific G4 antibody (BG4), establishes a direct correlation between cytotoxicity and the varying extent of G4 induction regulated by the two isoforms. Finally, we demonstrate the photo‐driven reversible regulation of G4 structures in lung cancer cells by Q‐Azo4F‐C. Our findings highlight the potential of light‐responsive G4‐binders in advancing precision cancer therapy through dynamic control of G4‐mediated pathways.

Unveiling the potential of lithium fluoride phosphate (Li2MPO4F, M = Fe, V, Mn) for the next generation of lithium-ion batteries: A comparative study based on first principles and molecular dynamic simulations

LiFePO4 (LFP) cathode with olivine crystal structure has been a key player in safe and affordable energy storage, owing to its low-cost iron and high electrochemical stability within a voltage range of commercial electrolytes (2.8–3.4 V). To maintain these benefits while enhancing its energy density, Li2MPO4F was developed by introducing fluorine (F) and replacing iron with other transition metals (M). However, previous studies on these materials primarily measured performance within a limited voltage window (e.g., 2.5–4.5 V), making it challenging to analyze their performance under advanced electrolytes with a broader voltage range. In this study, we took a novel approach by utilizing first principles and molecular dynamic calculations to investigate the electrochemical performance of Li2MPO4F with three types of transition metals (M = V, Fe, Mn). This unique methodology, which includes calculations on theoretical voltages, atomic structures, and diffusion coefficient after structural optimization, allowed us to predict the impact of transition metals on cathode performance. By closely comparing the expected results, this study discusses the pros and cons of each cation substitution and suggests suitable cathode materials for batteries with high energy density and superior rate capability.

Memprot.GPCR-ModSim: Modelling and simulation of membrane proteins in a nutshell.

Memprot.GPCR-ModSim leverages our previous web-based protocol, which was limited to class-A G protein-coupled receptors, to become the first one-stop web server for the modelling and simulation of any membrane protein system. Motivated by the exponential growth of experimental structures and the breakthrough of deep-learning-based structural modelling, the server accepts as input either a membrane-protein sequence, in which case it reports the associated AlphaFold model, or a 3D (experimental, modelled) structure, including quaternary complexes with associated proteins and/or ligands of any kind. In both cases, the molecular dynamics (MD) protocol produces a membrane-embedded, solvated, and equilibrated system, ready to be used as a starting point for further MD simulations, including ligand-binding free energy calculations. Memprot.GPCR-ModSim web server is publicly available at https://memprot.gpcr-modsim.org/. The standalone modules for 3D modelling (PyModSim) or membrane embedding and MD equilibration (PyMemDyn) are available at the GitHub repository https://github.com/GPCR-ModSim/. Supplementary data are available at Bioinformatics online.

Temperature-Dependent Trimethylamine N-Oxide Induced the Formation of Substance P Dimers.

Interactions of the peptide substance P (SP) (RPKPQQFFGLM-NH2) with trimethylamine N-oxide (TMAO) were investigated by using cryo-ion mobility-mass spectrometry (cryo-IM-MS), variable-temperature (278-358 K) electrospray ionization (vT-ESI) MS, and molecular dynamics (MD) simulations. Cryo-IM-MS provides evidence that cold solutions containing SP and TMAO yield abundant hydrated SP dimer ions, but dimer formation is inhibited in solutions that also contain urea. In addition, we show that SP dimer formation at cold solution temperatures (<298 K) is favored when TMAO interacts with the hydrophobic C-terminus of SP and is subject to reduced entropic penalty when compared to warmer solution conditions (>298 K). MD simulations show that TMAO lowers the free energy barrier for dimerization and that monomers dimerize by forming hydrogen bonds (HBs). Moreover, differences in oligomer abundances for SP mutants (P4A, P2,4A, G9P, and P2,4A/G9P) provide evidence that oligomerization facilitated by TMAO is sensitive to the cis/trans orientation of residues at positions 2, 4, and 9.

Deciphering significant interaction between Clp1 (CF IA) and Ssu72 (CPF) in pre-mRNA processing via in silico approaches

The cleavage and polyadenylation step are indispensable for pre-mRNA processing in eukaryotes. Defective 3′- end maturation of precursor mRNA has catastrophic effects, leading to several diseases in humans. This processing is orchestrated by a complex machinery comprising more than 20 proteins in Saccharomyces cerevisiae. Endonucleolytic cleavage followed by the addition of poly(A) tail at the 3′-end of the precursor mRNA requires CPF, CF IA and CF IB proteins. Clp1, a protein factor of the CF IA sub-unit is indispensable for the functioning of this machinery. Based on in silico analysis including molecular docking via different docking servers and molecular dynamics (MD) simulations, the current study provides key evidence of the Clp1 N-terminal (1–100 amino acids) domain’s interaction with Ssu72. MD simulations consolidate this binding between Clp1 and Ssu72. Our study presents strong evidence of a model where Clp1 (CF IA) associates with Ssu72 (CPF) and both the proteins are vital for tethering the complex for mediating cleavage and polyadenylation reaction during the key events of pre-mRNA 3′-end processing. These findings may pave the way to decipher the individual roles of Clp1 and Ssu72 during pre-mRNA maturation.

The Mechanism of Aluminum Deposition and Dendrite Growth on a Copper Substrate in Anode-Free Aluminum Batteries.

Given the critical demand for batteries with a high energy density and the global scarcity of lithium, anode-free aluminum batteries (AFABs) have attracted significant attention. AFABs utilize collectors instead of traditional anode metal foils, eliminating the need for anode materials and significantly enhancing the energy density of the batteries. However, the proliferation of aluminum dendrites might cause safety risks and reduce Coulombic efficiency, possibly impeding commercialization. This study employs molecular dynamics (MD) simulations to explore the deposition mechanisms of aluminum (Al) on copper (Cu) collectors and the dynamics of aluminum dendrite growth under nonhomogeneous deposition conditions. The results indicate that the surface properties of the Cu substrate significantly affect aluminum deposition, leading to more homogeneous and amorphous deposition on Cu(110) surfaces. However, the FCC structure of Al atoms on the Cu(111) surfaces exhibited the largest number. Strategically increasing the temperature and pressure can effectively prevent the formation of aluminum dendrites. The results are helpful for enhancing the battery cycle stability and the application of novel AFABs.

Structural and functional consequences of non-synonymous SNPs within the LAMA2 protein: a molecular dynamics perspective

Clinical phenotypic presentations associated with LAMA2 deficiency have shown a variety of manifestations. LAMA2 mutations are mainly linked to congenital muscular dystrophy, but there is also mounting evidence suggesting their presence in inflammatory breast cancer, laryngopharyngeal squamous cell carcinoma, and ventricular tachycardia related to coronary artery disease and cardiomyopathy. This study examined the structural and functional impacts of 144 non-synonymous single nucleotide polymorphisms (nsSNPs) within the LAMA2 gene. Through multi-tiered sequence and structure-based methods, 11 deleterious and destabilizing mutations were identified (A1362T, E1308Q, E1360G, I1276S, L1195P, M1359T, P1232H, P1238A, P1272L, Y1234H, Y1338C). Further, four mutations (L1195P, Y1234H, P1238A, A1362T), which aligned with conserved positions, were subjected to 500 ns molecular dynamics (MD) simulations. RMSD calculated from MD trajectories highlighted structural disparities between wild-type and mutant forms, with the latter showing greater flexibility. Radius of gyration analysis indicated reduced compactness, solvent accessibility changes suggested unfolding, and hydrogen bond (HB) analysis demonstrated disrupted integrity. The HB analysis revealed disruptions in structural integrity due to diminished hydrogen bonds in mutants. Secondary structure analysis revealed significant alterations in secondary structural content. Principal Component Analysis unveiled increased dynamic behavior in mutants. Gibbs free energy landscape analysis reflected distinct energy minima regions in mutants, indicating structural destabilization. Overall, this study revealed the functional and structural ramifications of nsSNPs in the LAMA2 gene, providing valuable insights into potential disease-causing mutations and warranting future research on understanding LAMA2 associated diseases and disorders.

Experimental and theoretical insights into the adsorption mechanism of methylene blue on the (002) WO3 surface

This work investigates the efficiency of green-synthesized WO3 nanoflakes for the removal of methylene blue dye. The synthesis of WO3 nanoflakes using Hyphaene thebaica fruit extract results in a material with a specific surface area of 13 m2/g and an average pore size of 19.3 nm. A combined theoretical and experimental study exhibits a complete understanding of the MB adsorption mechanism onto WO3 nanoflakes. Adsorption studies revealed a maximum methylene blue adsorption capacity of 78.14 mg/g. The pseudo-second-order model was the best to describe the adsorption kinetics with a correlation coefficient (R2) of 0.99, suggesting chemisorption. The intra-particle diffusion study supported a two-stage process involving surface adsorption and intra-particle diffusion. Molecular dynamic simulations confirmes the electrostatic attraction mechanism between MB and the (002) WO3 surface, with the most favorable adsorption energy calculated as -0.68 eV. The electrokinetic study confirmed that the WO3 nanoflakes have a strongly negative zeta potential of -31.5 mV and a uniform particle size of around 510 nm. The analysis of adsorption isotherms exhibits a complex adsorption mechanism between WO3 and MB, involving both electrostatic attraction and physical adsorption. The WO3 nanoflakes maintained 90% of their adsorption efficiency after five cycles, according to the reusability tests.

Target-centric analysis of hepatitis B: identifying key molecules and pathways for treatment

Hepatitis B virus (HBV) poses a significant global health challenge, potentially leading to severe liver conditions, with currently limited effective treatment options available. Xiao-Chai-Hu-Tang (XCHT), a well-known Traditional Chinese Medicine (TCM) prescription, shows promise in clinical trials for treating HBV. Therefore, screening the complex components of XCHT, identifying the active compounds, and closely exploring the targets associated with hepatitis B may constitute an effective strategy for the development of new therapeutic drugs for the treatment of this disease. A systematic pharmacology and GEO chip analysis identified key targets and pathways for hepatitis B treatment and effective ingredients. Molecular docking and molecular dynamics simulation techniques were used to explore the affinity and stability of active compounds with core targets, while assessing the druggability and safety of the active compounds. The therapeutic effect of the active compound protoporphyrin in XCHT on hepatitis B were mediated through key targets such as AKT1, MAPK1, and LCK, as well as key signaling pathways like PI3K-Akt signaling pathway and Ras signaling pathway. Protoporphyrin effectively bond to active pockets of core targets and demonstrated favorable druggability and a high safety threshold. The study provided valuable insights into the development of effective treatments for hepatitis B.