Molecular Dynamics Simulation Study Research Articles

C-di-GMP inhibits rRNA methylation and impairs ribosome assembly in the presence of kanamycin.

Cyclic diguanosine monophosphate (c-di-GMP) is a ubiquitous bacterial secondary messenger with diverse functions. A previous Escherichia coli proteome microarray identified that c-di-GMP binds to the 23S rRNA methyltransferases RlmI and RlmE. Here we show that c-di-GMP inhibits RlmI activity in rRNA methylation assays, and that it modulates ribosome assembly in the presence of kanamycin. Molecular dynamics simulation and mutagenesis studies reveal that c-di-GMP binds to RlmI at residues R64, R103, G114, and K201. Structural simulations indicate that c-di-GMP quenches RlmI activity by inducing the closure of the catalytic pocket. We also show that c-di-GMP promotes antibiotic tolerance through RlmI. Binding and methylation assays indicate that the inhibitory effect of c-di-GMP on RlmI is conserved across various pathogenic bacteria. Our data suggest an unexpected role for c-di-GMP in regulating ribosome assembly under stress through the inhibition of rRNA methyltransferases.

D-glucose-conjugated thioureas containing 2-aminopyrimidine as potential multitarget inhibitors for type 2 diabetes mellitus: Synthesis and biological activity study.

α-d-Glucose-conjugated thioureas 8a-w of substituted 4,6-diaryl-2-aminopyrimindines were designed, synthesized, and screened for their antidiabetic inhibitory activity. The thioureas with the strongest potential inhibitory activity included 8f (IC50=11.32±0.34μM for α-amylase), 8g (IC50=10.35±0.88μM for α-glucosidase), 8e (IC50=2.53±0.03nM for DPP-4), and 8c (IC50=3.93±0.03nM for PTP1B). The inhibitors 8g, 8e, and 8c were competitive α-glucosidase, non-competitive DDP-4, and non-competitive PTP1B inhibitors, respectively. In addition, compounds 8a, 8c, 8e, 8f, 8g, 8h, and 8j were noncytotoxic for 3T3 cell line. Induced fit docking study showed the key active interactions of each ligand with residues in the active site of each of these enzymes. Molecular dynamics simulation study on the representative complexes 8f/4W93 and 8e/3W2T in enzymes 4W93 and 3W2T, respectively, displayed the bioactive interactions between the residues and the corresponding potent inhibitor in the active site. Some of the various effects of the electron-donating and electron-withdrawing substituents on benzene of pyrimidine ring to inhibitory activities against enzymes related to T2DM were discussed. The calculations based on MM-GBSA showed the effects of the solvation to the active binding of the specific ligand in the active pocket of an enzyme.

In vivo and in silico study of europinidin against streptozotocin-isoproterenol-induced myocardial damage via alteration of hs-CRP/CPK-MB/Caspase-3/Bcl-2 pathways

Europinidin is a novel anthocyanidin found in the petals of Plumbago europea that exhibits several physiological effects. Research was conducted to assess europinidin’s cardioprotective efficacy in a diabetic and myocardial infarction (MI) experimental model. Rat was injected through the intraperitoneal administration of 45 mg/kg of streptozotocin (STZ), while MI was induced by subcutaneously administering 85 mg/kg of isoproterenol (ISP) at 24 and 48 h prior to the sacrifice procedure. Europinidin 10 and 20 mg/day was administered orally for 4 weeks after validation of diabetes (glucose > 250 mg/dl) on the 7th day. Experimental rats were randomly allocated to control, STZ-ISP control, STZ-ISP + europinidin-10 mg, STZ-ISP + europinidin-20 mg and europinidin 20 mg perse group. Biochemicals parameters including anti-diabetic (Glucose, HbA1c, serum insulin), cardiac markers (hs-CRP, CPK-MB), dyslipidaemia (lipid analysis), anti-inflammatory (IL6, TNF-α and IL-β), oxidative stress (MDA) and antioxidant (SOD, CAT and GSH), kidney function (creatinine), liver function (AST) and pancreatic function (lipase) along with apoptosis markers (Bcl-2, caspase-3) were evaluated. In addition, histopathological indices of heart injury were investigated. In addition, molecular docking (AUTODOCK Tools 1.5.6.) and dynamics were performed. Europinidin (10 and 20 mg/day) reduced blood glucose, HbA1c, hs-CRP, and CPK-MB. It improved serum insulin, blood lipid profile and reduced inflammatory cytokines (IL-6, TNF-α, IL-β), oxidative stress and increased antioxidant enzymes (SOD, CAT and GSH). Europinidin also protected renal, hepatic functions and restored apoptosis markers (increased Bcl-2, decreased caspase-3 levels). Histopathological analysis demonstrated a reduced extent of myocardial necrosis and fibrosis. Europinidin binds in silico to proteins 1NME, 1I0E, 3I2Y and 4AQ3 with energies of -7.038, -6.682, -8.6 and − 8.761 kcal/mol, respectively. While molecular dynamics simulation studies supported the interactions of europinidin with important therapeutic target proteins. Europinidin demonstrates significant cardioprotective and anti-diabetic potential in a diabetic MI experimental model.

Synergistic effect of tannic acid/stearic acid/calcium carbonate/recycled polypropylene polymer composites and molecular dynamics simulation study

AbstractDeveloping high‐toughness recycled polypropylene (REPP) composites using non‐polluting and cost‐effective methods remains a major challenge. In this study, we propose a novel modification scheme using tannic acid (TA)/stearic acid (SA) synergistically modified CC as a filler to prepare composites by blending with REPP. Characterizations, such as mechanical tests and thermodynamic tests, verified that the CC‐TA‐SA modified composites presented higher tensile and impact strengths as well as crystallinity. The tensile strength of the composites was increased from 27.44 to 30.53 MPa and similarly the impact strength was increased from 10.63 to 24.81 MPa. The thermal stability and melt fluidity of the modified composites also improved. This phenomenon is further investigated through the use of molecular dynamics (MD) simulations. This research expands the promise of REPP composites for industrial applications with stringent toughness requirements.Highlights Tannic/stearic acids modulate the surface properties of calcium carbonate. Polymer composite reinforced with synergistically modified calcium carbonate. Molecular dynamics simulations to predict composite properties.

Assessing the efficacy of iso-mukaadial acetate and betulinic acid against selected Plasmodium falciparum glycolytic pathway proteins: in silico and in vitro studies

Malaria is the extensive health concern in sub-Saharan Africa, with Plasmodium falciparum being the most lethal strain. The continued emergence of drug-resistant P. falciparum advocates for the development of new antimalarials. Our current study aimed to effectively explore the interaction capabilities of iso-mukaadial acetate (IMA) and betulinic acid (BA) against two essential P. falciparum glycolytic pathway proteins, PfLDH and PfHk. Recombinant PfLDH and PfHk were independently expressed in E. coli BL21 (DE3) cells and subsequently purified using affinity chromatography. Protein–ligand interaction studies probed in silico and in vitro approaches. Parasite inhibition studies confirmed potent antimalarial activity against the P. falciparum NF54 strains, with BA and IMA showing IC50 values of 1.27 µg/ml and 1.03 µg/ml against the asexual stage of P. falciparum, respectively. FTIR experiments confirmed interactions between the compounds and the secondary structure of the proteins. Direct protein–ligand interaction studies analysis using microscale thermophoresis (MST) showed a KD value of 0.1036 ± 0.6001 µM for the PfLDH-BA complex and 0.7473 ± 0.3554 µM KD value for PfLDH-IMA. Meanwhile, PfHk-IMA had 0.39701 ± 0.16298 µM KD value, while the PfHk-BA complex had no interaction detected. Molecular docking and molecular dynamics simulation studies were used to measure and confirm the interactive strength of complexes. Molecular docking reported a binding score of − 1.155 kcal/mol for the PfLDH-BA complex and a binding score of − 3.200 kcal/mol for PfLDH-IMA. The PfHk-BA complex had − 2.871 kcal/mol and PfHk-IMA complex had − 4.225 kcal/mol binding score. In conclusion, BA and IMA compounds had better interactions and remained bound within the binding sites of the glycolytic pathway proteins (PfLDH and PfHk).

Biological Effects of Calceolarioside A as a Natural Compound: Anti-Ovarian Cancer, Anti-Tyrosinase, and Anti-HMG-CoA Reductase Potentials with Molecular Docking and Dynamics Simulation Studies.

One kind of hydroxycinnamic acid is calceolarioside A. Plantago coronopus, Cassinopsis madagascariensis, and other organisms for whom data are available are known to have this naturally occurring compound. IC50 values of Calceolarioside A for ovarian cell lines (NIH-OVCAR-3, ES-2, UACC-1598, Hs832.Tc, TOV-21G, UWB1.289) were 24.42, 13.50, 9.31, 14.90, 20.07, and 16.18µM, respectively. IC50 values were 19.83 and 73.48µM for tyrosinase and HMG-CoA reductase enzymes. The chemical activities of Calceolarioside A against HMG-CoA reductase and tyrosinase were assessed by conducting the molecular docking study, MM/GBSA calculation, and molecular dynamics (MD) simulation. The anticancer activities of this compound were evaluated against some ovarian cancer cells, such as NIH-OVCAR-3, ES-2, UACC-1598, Hs832.Tc, TOV-21G, and UWB1.289 cell lines. The chemical activities of Calceolarioside A against some of the expressed surface receptor proteins (folate receptor, CD44, EGFR, Formyl Peptide Receptor-Like 1, M2 muscarinic receptor, and estrogen receptors) were investigated using computational methods. The results exhibited the interplay among atoms. The compound formed robust associations with both the enzymes and receptors. Calceolarioside A can hinder the functioning of these enzymes and the proliferation of malignant cells.

Exploring Dynamics and Intermolecular Interactions in Binary Mixtures of Reline and DMSO: An Investigation Using Nuclear Magnetic Resonance and Infrared Spectroscopic Techniques.

Reline, which is composed of choline chloride and urea in a molar ratio of 1:2, is the first and most extensively studied deep eutectic solvent (DES). In certain applications, reline is blended with organic solvents, dimethyl sulfoxide (DMSO) in most cases, to gain improved properties. Therefore, it is crucial to have a profound understanding of the impact of DMSO on the dynamics and structures of the species in the binary mixtures. In this study, neat reline and ten reline/DMSO mixtures, with DMSO molar fraction ranging from 0.1 to 0.95, were investigated primarily through a combined approach utilizing nuclear magnetic resonance (NMR) and Fourier transform infrared (FT-IR) spectroscopic techniques. Based on our investigation, we probed a significant transition of the binary mixtures from large molecule solutions or viscous liquids to nonviscous small-molecule solutions at a DMSO molar fraction of 0.7. Specifically, upon analyzing the self-diffusion coefficient, 1H T1 and 1H T2, we observed a notable increase in the molecular mobility of the species within the reline/DMSO system, particularly when the DMSO molar fraction exceeded 0.7. Drawing upon the FT-IR findings, we suggest that the enhanced molecular mobility, as evidenced by NMR analysis, is correlated with the disruption of molecular hydrogen-bonding interactions involving the -NH2 and -OH groups. Furthermore, based on 1D 1H, 1D 15N, and 2D 1H-1H COSY spectra, it was revealed that the interaction between urea and choline remains relatively stable until the DMSO fraction exceeds 0.7, whereupon it exhibited a notable weakening as the DMSO fraction increases from 0.7 to 0.95. In the meantime, DMSO molecules predominantly engage in hydrogen bond interactions with urea and choline when the DMSO molar fraction exceeds 0.7. Our results align well with previous molecular dynamics (MD) simulation studies and provide profound insights into the significant transition in the reline/DMSO mixture system.

Novel tetracycline hybrids: synthesis, characterization, docking studies and in-vitro evaluation of antibacterial activity

BackgroundThe biggest menace in the world today is the infection caused by pathogenic bacteria in humans, where majority of the available antibiotics fail to provide therapeutic results due to resistance. The discovery of new molecules is the need of the hour and several research groups worldwide are contributing to fight this scare. This work highlights our efforts towards discovering novel tetracycline hybrids that could serve as potent agents against several pathogenic bacterial strains causing infections. In total, ten compounds were synthesized which were chemically conjugates of Minocycline, an age-old tetracycline, and naturally occurring aldehydes and ketones available from the plant sources. Structural characterization of these compounds was done using Mass and 1HNMR. Molecular docking was carried out in order to predict the binding affinity of these compounds to various bacterial enzymes and known protein targets and to establish the structure–activity relationships. Molecular dynamic simulation studies and in silico pharmacokinetic and toxicity prediction studies were done to determine in silico pharmacokinetics and toxicity of compounds. In-vitro antibacterial activities were done using standard protocols against gram positive bacteria like Enterococcus faecalis, Staphylococcus aureus and gram-negative bacteria like Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli.ResultsPromising results were obtained viz. compound 1,2 and 10 were found to be more potent against Staphylococcus aureus, compound 1 against Enterococcus faecalis, compound 2 and 3 against Escherichia coli, compound 7 and 8 against Pseudomonas aeruginosa and compound 7 against Klebsiella pneumoniae when compared with minocycline as standard compound.ConclusionAll the synthesized compounds were screened for their anti-bacterial activity against gram positive and gram negative microorganisms. Amongst the ten synthesized minocycline hybrids, four minocycline hybrids exhibited potent antibacterial activity as compared to minocycline. These hybrids can serve as a promising lead compound for antibiotic drug discovery.

Discovering potential ERK1 inhibitors from natural products for therapeutic targeting of Alzheimer's disease.

Extracellular signal-regulated kinase 1 (ERK1) belongs to mitogen-activated protein kinases, which are essential for memory formation, cognitive function, and synaptic plasticity. During Alzheimer's disease (AD), ERK1 phosphorylates tau at 15 phosphorylation sites, leading to the formation of neurofibrillary tangles. The overactivation of ERK1 in microglia promotes the release of pro-inflammatory cytokines, which results in neuroinflammation. Additionally, elevated oxidative stress during AD stimulates the ERK1 pathway, leading to neuronal loss. Because ERK1 signaling plays a significant role in tau phosphorylation, targeting ERK1 may be therapeutically beneficial by either preventing excessive activation of the signaling pathway or altering its pathway to enhance neuroprotective effects during AD. This study employed structure-based virtual screening of phytoconstituents from the IMPPAT library. Subsequently, in-depth docking and molecular dynamics (MD) simulation studies were implemented to identify potential ERK1 inhibitors with desirable pharmacological properties. Silandrin and Hydroxytuberosone were found to be potential ERK1 inhibitors with higher affinity and specificity than the control molecule Tizaterkib. These compounds specifically bind to the ERK1 substrate binding pocket and interact with crucial residues. Finally, the elucidated compounds with ERK1 were evaluated using an all-atom molecular MD simulation to analyze structural dynamics, structural compactness, hydrogen bond dynamics, principal component analysis, and free energy landscape. The study suggested that Silandrin and Hydroxytuberosone can further be exploited as potential lead molecules for therapeutic development against ERK1-mediated AD.

Molecular dynamic simulation study on the influence of heating rate on the thermal decomposition process of 1,3,5-triamino-2,4,6-trinitrobenzene (TATB).

To clarify the effect of heating rate on the thermal decomposition process of 1,3,5-triamino-2,4,6-trinitrobenzene (TATB), this study employs molecular dynamic simulations to investigate the thermal decomposition of TATB at heating rates of 20, 40, 60, and 80K/ps. The initial temperature is uniformly set to 300K, while the final temperature is set to 3000K. Results indicate that within the temperature range of 300-3000K, the thermal decomposition rate of TATB decreases with increasing heating rate, whereas the initial decomposition temperature of TATB increases, consistent with the experimental pattern. Within the studied temperature range, a lower heating rate results in a higher number of decomposition fragments, leading to more effective collision between active fragments, facilitating more effective collisions between active species, and leading to the formation of more stable products such as H₂O, CO₂, and N₂. Conversely, higher heating rates reduce the quantities of these stable products. This study enhances the understanding of TATB's thermal decomposition mechanism, providing valuable insights for its safe handling and application. METHODS: The Gaussian09 software was used to calculate the BDEs of TATB molecules, while the MD simulation using the ReaxFF-lg force field was performed by the LAMMPS package. Visualization and postprocessing were conducted using the OVITO software, and a custom script was developed to analyze the reaction products and frequencies.

How Binding Site Flexibility Promotes RNA Scanning by TbRGG2 RRM: A Molecular Dynamics Simulation Study.

RNA recognition motifs (RRMs) are a key class of proteins that primarily bind single-stranded RNAs. In this study, we applied standard atomistic molecular dynamics simulations to obtain insights into the intricate binding dynamics between uridine-rich RNAs and TbRGG2 RRM using the recently developed OL3-Stafix AMBER force field, which improves the description of single-stranded RNA molecules. Complementing structural experiments that unveil a primary binding mode with a single uridine bound, our simulations uncover two supplementary binding modes in which adjacent nucleotides encroach upon the binding pocket. This leads to a unique molecular mechanism through which the TbRGG2 RRM is capable of rapidly transitioning the U-rich sequence. In contrast, the presence of non-native cytidines induces stalling and destabilization of the complex. By leveraging extensive equilibrium dynamics and a large variety of binding states, TbRGG2 RRM effectively expedites diffusion along the RNA substrate while ensuring robust selectivity for U-rich sequences despite featuring a solitary binding pocket. We further substantiate our description of the complex dynamics by simulating the fully spontaneous association process of U-rich sequences to the TbRGG2 RRM. Our study highlights the critical role of dynamics and auxiliary binding states in interface dynamics employed by RNA-binding proteins, which is not readily apparent in traditional structural studies but could represent a general type of binding strategy employed by many RNA-binding proteins.

In-silico study of E169G and F242K double mutations in leucine-rich repeats (LRR) polygalacturonase inhibiting protein (PGIP) of Gossypium barbadense and associated defense mechanism against plant pathogens

BackgroundPolygalacturonase inhibiting proteins (PGIPs) play a pivotal role in plant defense against plant pathogens by inhibiting polygalacturonase (PG), an enzyme produced by pathogens to degrade plant cell wall pectin. PGIPs, also known as leucine-rich repeat pathogenesis-related (PR) proteins, activate the host’s defense response upon interaction with PG, thereby reinforcing the host defense against plant pathogens attacks. In Egyptian or extra-long staple cotton (Gossypium barbadense), the interaction between PGIP and PG is one of the crucial steps in the defense mechanism against major pathogens such as Xanthomonas citri pv. malvacearum and Alternaria macrospora, which are responsible for bacterial leaf blight and leaf spot diseases, respectively.ResultsTo unravel the molecular mechanisms underlying these PR proteins, we conducted a comprehensive study involving molecular modeling, protein-protein docking, site-specific double mutation (E169G and F242K), and molecular dynamics simulations. Both wild-type and mutated cotton PGIPs were examined in the interaction with the PG enzyme of a bacterial and fungal pathogen. Our findings revealed that changes in conformations of double-mutated residues in the active site of PGIP lead to the inhibition of PG binding. The molecular dynamics simulation studies provide insights into the dynamic behaviour and stability of the PGIP-PG complexes, shedding light on the intricate details of the inhibitory and exhibitory mechanism against the major fungal and bacterial pathogens of G. barbadense, respectively.ConclusionsThe findings of this study not only enhance our understanding of the molecular interactions between PGs of Xanthomonas citri pv. malvacearum and Alternaria macrospora and PGIP of G. barbadense but also present a potential strategy for developing the disease-resistant cotton varieties. By variations in the binding affinities of PGs through specific mutations in PGIP, this research offers promising avenues for the development of enhanced resistance to cotton plants against bacterial leaf blight and leaf spot diseases.

Design, synthesis, in vitro evaluation, and molecular dynamics simulation studies of novel coumarin-acetohydrazide Schiff base derivatives as urease enzyme inhibitors

Design, synthesis, in vitro evaluation, and molecular dynamics simulation studies of novel coumarin-acetohydrazide Schiff base derivatives as urease enzyme inhibitors

Multipotent Effect of Clozapine on Lipopolysaccharide-Induced Acetylcholinesterase, Cyclooxygenase-2,5-Lipoxygenase, and Caspase-3: In Vivo and Molecular Modeling Studies.

Dual inhibition of cyclooxygenase-2 (COX-2) and lipoxygenase (LOX) is a recognized strategy for enhanced anti-inflammatory effects in small molecules, offering potential therapeutic benefits for individuals at risk of dementia, particularly those with neurodegenerative diseases, common cancers, and diabetes type. Alzheimer's disease (AD) is the most common cause of dementia, and the inhibition of acetylcholinesterase (AChE) is a key approach in treating AD. Meanwhile, Caspase-3 catalyzes early events in apoptosis, contributing to neurodegeneration and subsequently AD. Structure-based virtual screening of US-FDA-approved molecules from the ZINC15 database identified clozapine (CLOZ) as the dual inhibitor of COX-2 and AChE, with significant binding affinity. Further molecular docking of CLOZ in the active site of LOX and Caspase-3 also showed significant binding potential. Further, the results from molecular docking were validated using molecular dynamics simulation (MDS) studies, confirming the results from molecular docking. The results from MDS showed good binding potential and interactions with key residues. The CLOZ was further assessed using lipopolysaccharide (LPS)-challenged rats treated for thirty days at doses of 5 and 10 mg/kg, p.o. The results demonstrated modulation of COX-2, 5-LOX, AChE, Caspase-3, and MDA in LPS-induced brains. Additionally, the expression level of IL-10 was also measured. Our results showed a significant decrease in the levels of COX-2, 5-LOX, AChE, Caspase-3, and MDA. Our results also showed a significant decrement in the pro-inflammatory markers NF-κB, TNF-α, and IL-6 and an improvement in the levels of anti-inflammatory markers IL-10 and TGF-β1. Overall, the findings indicate that CLOZ has potential for neuroprotective effects against LPS-treated rats and can be explored.

Development of Benzimidazole Anticancer Leads for EGFR Inhibition by 3D-QSAR Based Virtual Screening, Molecular Docking, Molecular Simulation and Drug Likeness Study

Background: Breast cancer is the most common cancer in women. Tyrosine kinase inhibitors were developed to treat breast cancer. EGFR/ErbB1 inhibition has proved to be a promising target in breast carcinoma therapy. Drugs with benzimidazole nucleus have been approved by the FDA for cancer treatment. Objective: To design and develop benzimidazole anticancer small molecules for EGFR inhibition for the treatment of breast cancer. Methods: By 3D-QSAR-based virtual screening, molecular docking, molecular simulation and drug likeness study. Results: In this research, a 3D-QSAR pharmacophore was generated with four salient features. Namely H-bond acceptor (HBA), two ring aromatic (RA) and hydrophobic (HY) features. Its correlation- coefficient (r) is 0.8412, RMSD of 0 .96 and with 32.84 bits cost difference value. With virtual screening, 4 top hits were identified. Novel benzimidazole derivatives were designed (1a-ll) by using the features of hit molecules and the pharmacophore. The novel designed small molecules that were druggable as they passed the Lipinski and Veber rule. Novel ligands and EGFR protein interaction were good. 1a and 1i were found to be the best-designed molecules. They had -8.6 Kcal/mol and -8.4 Kcal/mol docking interaction energy, respectively, whereas Compound 4 (reference) scored -7.4 Kcal/mol. Both these molecules were stable inside the binding pocket of the EGFR protein. The molecular dynamic simulation study revealed that 1a attained equilibrium at 0.15nm. Conclusion: In silicon novel benzimidazole small molecules were designed and developed as EGFR inhibitors to treat breast cancer.

Computational Evaluation of Punica granatum Leaf Phytochemicals against Multi-drug Resistant E. coli: Molecular Docking, ADMET, MD Simulation, and DFT Studies.

Multidrug-resistant (MDR) E. coli presents a significant challenge in clinical settings, necessitating the exploration of novel therapeutic agents. Phytochemicals from Punica granatum (pomegranate) leaves have shown potential antibacterial properties. This study aims to identify and evaluate the efficacy of these phytochemicals against MDR E. coli. This study aims to identify and evaluate the efficacy of most potential phytochemical of Punica granatum leaf against MDR E. coli. through molecular docking, adme, toxicity, molecular dynamic simulation, MMPBSA and DFT approaches. We performed molecular docking of 11 phytochemicals from the IMPPAT database with four MDR E. coli targets: 1AJ6, 1FJ8, 4BJP, and 6BU3. Granatin B demonstrated the best binding affinity and was further analyzed. ADME (Absorption, Distribution, Metabolism, and Excretion) and toxicity analyses were conducted to assess its pharmacokinetic properties and safety profile. Molecular Dynamics (MD) simulations were performed to evaluate the stability of Granatin B with the targets. Finally, density functional theory (DFT) analysis was carried out to understand the electronic properties and reactivity of Granatin B. Granatin B exhibited the highest binding affinity among the 11 phytochemicals, indicating strong potential as an inhibitor of MDR E. coli. ADME analysis revealed favorable pharmacokinetic properties and toxicity analysis confirmed that Granatin B is non-toxic. MD simulations showed stable interactions between Granatin B and all four targets. DFT analysis provided insights into the electronic properties and reactive sites of Granatin B, supporting its potential mechanism of action. Granatin B from Punica granatum leaves is a promising candidate for treating MDR E. coli infections. The integration of molecular docking, ADME, toxicity, MD simulations, and DFT analysis underscores its therapeutic potential and paves the way for further experimental validation and development as a novel antibacterial agent.

Low-density Lipoprotein as an Endogenous Cancer-Targeting Carrier for Cholesterol-Drug Delivery: A Molecular Dynamics Simulation Study

Low-density Lipoprotein as an Endogenous Cancer-Targeting Carrier for Cholesterol-Drug Delivery: A Molecular Dynamics Simulation Study

Molecular Dynamics Simulation Study on Heterogeneous Structure, Rheology, and Dynamic Correlation of Concentrated Aqueous Solutions of a Lithium Salt.

Molecular dynamics simulation of an aqueous solution of lithium bis(trifluoromethanesulfonyl)amide, LiTFSA, was performed at various concentrations to relate its liquid structure with frequency-dependent shear viscosity. The structure factor exhibited a low-q peak that represents a heterogeneous structure composed of water and anion domains, and the lithium ion existed in the water domain due to its strong hydration. The frequency-dependent shear viscosity showed bimodal relaxation, and the relative contribution of the slower mode increased with an increase in the salt concentration. The cross-correlation between the shear stress and the two-body density revealed that the slower viscoelastic mode is assigned to the dynamics of the heterogeneous structure, and the assignment was also confirmed by the comparison between the viscoelastic and structural relaxations. The collective translational motions of the cation and the anion showed a strong negative correlation in a concentrated solution, reflecting the heterogeneous domain structure.

Efficient adsorption of ofloxacin in a novel nanocomposite formed by nano-hexagonal boron nitride fused with zeolite imidazolite skeleton-8: Experimental and molecular dynamics simulation studies.

With the widespread application of antibiotics in the medical field, associated wastewater pollution has become a critical environmental issue, creating potential risks to ecosystems and public health. This study synthesized three novel nanocomposite materials, ZIF-8@h-BN-X, using an in-situ growth method by adjusting h-BN content. Compared to pure two-dimensional hexagonal boron nitride (h-BN), their adsorption capacities for ofloxacin (OFL) in solution were evaluated. Results showed that zeolitic imidazolate framework-8 (ZIF-8) attached and grew on the h-BN surface, altering surface functional groups and significantly enhancing the nanocomposite's adsorption effect on OFL. Adsorption capacity depended on the initial h-BN content, with lower X content resulting in more active sites and stronger adsorption capacity. Equilibrium adsorption capacities were 145.46, 124.91, and 58.16 mg·g-1 for X values of 29.82 %, 45.93 %, and 62.95 %, respectively. Molecular dynamics simulations revealed interaction energies of -109.13 kcal·mol-1 between ZIF-8@h-BN-X and OFL, compared to -84.78 kcal·mol-1 between pure h-BN and OFL, demonstrating the superior adsorption performance of ZIF-8@h-BN-X. OFL adsorption on ZIF-8@h-BN-X followed the Langmuir isotherm model and pseudo-second-order adsorption kinetics. Thermodynamic parameters indicated that the adsorption process of ZIF-8@h-BN-X was exothermic and spontaneous when compared to h-BN alone. This study highlights the significant potential of ZIF-8@h-BN-X in treating antibiotic-contaminated wastewater, while providing theoretical and practical insights for developing novel, efficient two-dimensional nanocomposite adsorbents.

Unravelling the Microscopic Interactions underlying Uranyl Species Adsorption by Charged COFs: A Molecular Dynamics Simulation Study

Unravelling the Microscopic Interactions underlying Uranyl Species Adsorption by Charged COFs: A Molecular Dynamics Simulation Study