Computational Insights Research Articles

Antimicrobial Potential of Selected Phytochemicals from Hygrophila schulli; Computational Insights

The escalating global concern over antibiotic resistance has led to an intensified exploration of alternative therapeutic strategies, including the utilization of plant-derived secondary metabolites. In this in-silico study, we investigated the structural inhibition of bacterial DNA Topoisomerase IV complex by major secondary metabolites extracted from the medicinal plant Hygrophila schulli. The plant is renowned for its rich phytochemical composition, possessing bioactive compounds with diverse pharmacological properties. Using computational approaches, we conducted molecular docking simulations to explore the binding affinities and interactions between the identified secondary metabolites from Hygrophila schulli and the target bacterial DNA Topoisomerase IV complex. Our results unveil promising interactions, suggesting a potential inhibitory effect on the targeted protein. Furthermore, molecular dynamics simulations were employed to examine the dynamic behavior of the ligand-protein complexes, providing insights into the stability and conformational changes over time. This in-silico exploration contributes valuable information to the understanding of the molecular interactions between plant-derived secondary metabolites and Bacterial DNA Topoisomerase IV, laying the groundwork for future experimental validations. The findings from this study may pave the way for the development of novel antimicrobial agents derived from natural sources, offering a sustainable and effective approach in the ongoing battle against antibiotic-resistant bacterial infections.

Novel Pyrazole-Chalcone Hybrids: Synthesis and Computational Insights Against Breast Cancer.

More women die of breast cancer than of any other malignancy. The resistance and toxicity of traditional hormone therapy created an urgent need for potential molecules for treating breast cancer effectively. Novel biphenyl-substituted pyrazole chalcones linked to a pyrrolidine ring were designed by using a hybridization approach. The hybrids were assessed against MCF-7 and MDA-MB-231 cells by NRU assay. Among them, 8 k, 8 d, 8 m, 8 h, and 8 f showed significantly potent IC50 values: 0.17, 5.48, 8.13, 20.51, and 23.61 μM) respectively, on MCF-7 cells compared to the positive control Raloxifene and Tamoxifen. Furthermore, most active compound 8 k [3-(3-(4-fluorophenyl)-1-phenyl-1H-pyrazol-4-yl)-1-(2-(2-(pyrrolidin-1-yl)-ethoxy)-phenyl)-chalcone] showed cell death induced through apoptosis, cell cycle arrest at the G2/M phase, and demonstrated decrease of ER-α protein in western blotting study. Docking studies of 8 k and 8 d established adequate interactions with estrogen receptor-α as required for SERM binding. The active hybrids exhibited good pharmacokinetic properties for oral bioavailability and drug-likeness. Whereas, RMSD, RMSF, and Rg values from Molecular dynamics studies stipulated stability of the complex formed between compound 8 k and receptor. All of these findings strongly indicate the antiproliferative potential of pyrazole-chalcone hybrids for the treatment of breast cancer.

Computational and spectroscopic insight into the binding of citral with human transferrin: Targeting neurodegenerative diseases

The involvement of neuroinflammation in the pathogenesis of neurodegenerative disorders (NDs) is very significant. Currently, only symptomatic treatments exist, and there are no drugs that modify the progression of Alzheimer's disease (AD) or other NDs. Consequently, there is increasing attention on addressing AD-related neuroinflammation using anti-inflammatory compounds and antioxidants. Currently, there is a growing exploration of dietary phytochemicals as potential therapeutic agents for treating inflammation. Citral, a monoterpene, is under increasing investigation due to its neuroprotective effects. The dysregulation of iron homeostasis is a crucial factor in supporting neuroinflammation, underscoring the significance of proper iron balance. Human transferrin (htf) is a major player involved in iron homeostasis. In this study, we examined binding and dynamics of htf–citral complex through diverse experimental methods. Molecular docking studies revealed that citral binds to crucial residues of htf, forming a stable complex. UV–visible spectroscopy demonstrated binding of citral with htf with good affinity, evident from binding constant of 1.48 × 105 M−1. Further, fluorescence spectroscopy entrenched a stable htf-citral complex formation; citral demonstrates an excellent binding affinity to htf with a binding constant of 106 M−1. Moreover, fluorescence binding assay at various temperatures deciphered htf-citral complex to be driven by both static and dynamic quenching. The analysis of enthalpy change (ΔH) and entropy change (ΔS) demonstrated that htf-citral complex formation was driven mainly by hydrophobic interactions.The current work gives a platform to develop innovative therapeutic strategies targeting neuroinflammation through citral, particularly iron homeostasis.

Destabilizing high-capacity high entropy hydrides via earth abundant substitutions: From predictions to experimental validation

The vast chemical space of high entropy alloys (HEAs) makes trial-and-error experimental approaches for materials discovery intractable and often necessitates data-driven and/or first principles computational insights to successfully target materials with desired properties. In the context of materials discovery for hydrogen storage applications, a theoretical prediction-experimental validation approach can vastly accelerate the search for substitution strategies to destabilize high-capacity hydrides based on benchmark HEAs, e.g. TiVNbCr alloys. Here, machine learning predictions, corroborated by density functional theory calculations, predict substantial hydride destabilization with increasing substitution of earth-abundant Fe content in the (TiVNb)75Cr25-xFex system. The as-prepared alloys crystallize in a single-phase bcc lattice for limited Fe content x < 7, while larger Fe content favors the formation of a secondary C14 Laves phase intermetallic. Short range order for alloys with x < 7 can be well described by a random distribution of atoms within the bcc lattice without lattice distortion. Hydrogen absorption experiments performed on selected alloys validate the predicted thermodynamic destabilization of the corresponding fcc hydrides and demonstrate promising lifecycle performance through reversible absorption/desorption. This demonstrates the potential of computationally expedited hydride discovery and points to further opportunities for optimizing bcc alloy ↔ fcc hydrides for practical hydrogen storage applications.

Comprehensive Analysis of Flow Dynamics and Pressure Variations in PEM Water Electrolyzers: Experimental and Computational Insights into Gas Diffusion Electrodes

Polymer Electrolyte Membrane Water Electrolyzers (PEMWEs) can produce green hydrogen with zero emission with renewable energy sources integration. The gas diffusion electrodes (GDEs) are one of the main components of PEMWE. In this study, the flow behavior of GDEs for different patterns like square GDE (SGDE), circle GDE (CGDE), equilateral triangle GDE (ETGDE), and rhombic GDE (RGDE) was investigated numerically and experimentally for different flow rates at 100 mL min−1, 200 mL min−1, and 300 mL min−1. In pressure drop (ΔP) and flow visualization experiments, SGDE showed the best performance. Experimental results were compared with each other by validating them in the numerical analysis of multiphase flow conditions. As a result, at 100 mL min−1 flow rate, the flow is directed to the outlet side with 38.96 % less pressure loss in SGDE geometry. In flow visualization experiments, at 100 mL min−1 flow rate, SGDE geometry fills the cell faster than other GDE geometries by 0.437 sec. The results from the ex-situ ink test performance of the GDEs were confirmed in electrochemical single cell PEMWE tests via Pt coated GDEs. Furthermore, SGDE exhibited superior performance in thein-situtests. In the numerical calculation results, when 16 % porosity filter paper was examined, it was concluded that the SGDE geometry was 94.8 % rate successfully carried the liquid phase to all geometry. It is supposed that water transfer inside the cell may be improved by using an SGDE for the anode GDE, and the performance of PEMWE could be increased by providing faster delivery of the oxygen gas and excess water to the outside of the cell.

Computational Insight into the Mechanism of Action of DNA Gyrase Inhibitors; Revealing a New Mechanism.

Discovery of novel antimicrobial agents is in need to deal with antibiotic resistance. Elucidating the mechanism of action for established drugs contributes to this endeavor. DNA gyrase is a therapeutic target used in the design and development of new antibacterial agents. Selective antibacterial gyrase inhibitors are available; however, resistance development against them is a big challenge. Hence, novel gyrase inhibitors with novel mechanisms are required. In this study, the mechanism of action for selected DNA gyrase inhibitors available was carried out through molecular docking and molecular dynamics (MD) simulation. In addition, pharmacophore analysis, density functional theory (DFT) calculations, and computational pharmacokinetics analysis of the gyrase inhibitors were performed. This study demonstrated that all the DNA gyrase inhibitors investigated, except compound 14, exhibit their activity by inhibiting gyrase B at a binding pocket. The interaction of the inhibitors at Lys103 was found to be essential for the binding. The molecular docking and MD simulation results revealed that compound 14 could act by inhibiting gyrase A. A pharmacophore model that consisted of the features that would help the inhibition effect was generated. The DFT analysis demonstrated 14 had relatively high chemical stability. Computational pharmacokinetics analysis revealed that most of the explored inhibitors were estimated to have good drug-like properties. Furthermore, most of the inhibitors were found to be non-mutagenic. In this study, mode of action elucidation through molecular docking and MD simulation, pharmacophore model generation, pharmacokinetic property prediction, and DFT study for selected DNA gyrase inhibitors were carried out. The outcomes of this study are anticipated to contribute to the design of novel gyrase inhibitors.

Computational insights into survival durations and prehospital interventions in accidental cold-water immersion: A comprehensive analysis of fresh and saltwater temperatures

This study examines the complex relationship between scenarios of cold-water immersion, survival durations, and prehospital interventions. It utilizes computational modeling methods to shed light on how different water temperatures affect individuals facing accidental cold-water immersion incidents. The analysis reveals significant variations in survival times based on water temperature. For example, subjects immersed in water at temperatures of 5 °C, 2 °C, and 0 °C had average survival times of 136, 113, and 100 min, respectively, under stable conditions. In flowing water at the same temperatures, survival times decreased to 119, 92, and 81 min, indicating the impact of water movement on cooling rates and survival durations. Likewise, individuals immersed in saltwater at temperatures of 5 °C, 2 °C, 0 °C, and −2 °C showed average survival times of 111, 88, 80, and 66 min, respectively, in static conditions. In flowing saltwater at the same temperatures, survival times decreased to 98, 74, 68, and 57 min, highlighting the influence of water flow on cooling rates and survival durations. A comparison between immersion in pure water and saltwater at 2 °C revealed survival times of 113 and 88 min under stable conditions and 92 and 74 min under dynamic conditions, emphasizing the role of water composition in survival outcomes. The study also challenges the notion that the demise of the Titanic's passengers and crew resulted from hypothermia, asserting instead that severe thermal shock was the primary cause. These numerical findings underscore the importance of considering water temperature, flow dynamics, and prompt medical responses in cold-water emergencies to enhance survival prospects. The study identifies water within the range of 41–43 °C as the most effective active external rewarming fluid for critical hypothermal conditions. By quantifying the impact of these variables on survival times, the study provides data-driven recommendations to improve emergency protocols and outcomes for individuals facing cold-water immersion incidents.

Computational insights and phase transition of ruthenium alloy by classical molecular dynamics simulations

Computational insights and phase transition of ruthenium alloy by classical molecular dynamics simulations

Experimental and Computational Insights into the Catalytic Mechanism of Y1-xBaxCoO3-δ Perovskite Oxides with a Controlled Crystal Structure.

The crystal structure of Co-based perovskite oxides (ACoO3) can be controlled by adjusting the A-site elements. In this study, we synthesized Y1-xBaxCoO3-δ (x = 0, 0.5, and 1.0) via a coprecipitation method and investigated their CO oxidation performances. YCoO3 (x = 0; cubic perovskite oxide; Pbnm) shows a higher catalytic performance than Y0.5Ba0.5CoO2.72 (x = 0.5; A-site-ordered double perovskite oxide; P4/nmm), which exhibits high oxygen nonstoichiometric properties, and BaCoO3 (x = 1.0; hexagonal perovskite oxide; P63/mmc), which contains high-valent Co4+ species. To elucidate the reaction mechanism, we conducted isotopic experiments with CO and 18O2. The CO oxidation reaction on YCoO3 proceeds via the Langmuir-Hinshelwood mechanism, which is a surface reaction of CO and O2 gas that does not utilize lattice oxygen. Because of the significantly smaller specific surface area of YCoO3 compared with that of the reference Pt/Al2O3, the bulk features of the crystal structures affect the catalytic reaction. When density functional theory is applied, YCoO3 clearly exhibits semiconducting properties in the ground state with the diamagnetic t2g6eg0 states, which can translate to a magnetic t2g5eg1 configuration upon excitation by a relatively low energy of 0.64 eV. We propose that the unique nature of YCoO3 activates oxygen in the gas phase, thereby enabling the smooth oxidation of CO. This study demonstrates that the bulk properties originating from the crystal structure contribute to the catalytic activity and reaction mechanism.

A comprehensive investigation of (E)-2,4-Dimethyl-6-(((2-(Phenylthio)phenyl)imino)methyl)phenol (2PTALD): Synthesis, crystal structure, and computational insights with molecular dynamic simulations

The titled compound (E)-2,4-Dimethyl-6-(((2-(Phenylthio)phenyl)imino)methyl)phenol (2PTALD) was synthesized followed by crystallization and characterized with NMR, UV and FTIR analysis. The crystal structure of 2PTALD revealed molecular geometry and compared with theoretical results and found comparable. Based on further calculations on the optimized structure - vibrational spectra, electronic characteristics and NMR spectra compared with experimental findings which given a very consistent match. MEP, ELF and thermodynamic parameters are given idea of reactivity and stability. The HOMO & LUMO found energies signifying a significant charge transfer inside the molecule. The molecular docking of 2PTALD was done with three most suitable protein with high values of binding energies. Dynamic simulations were performed using an 8W4S protein target, and analysed interaction of ligand with protein in details. Hirshfeld surface analysis offered a comprehensive visualization of intermolecular associates in the crystal structure of 2PTALD. Overall, study presents a comprehensive investigation of Schiff base ligand 2PTALD, combining experimental and computational approaches to characterize its structure, properties, and potential applications.

Computational Insights into Dion-Jacobson Type Oxide Ion Conductors.

Dion-Jacobson type materials have recently emerged as a new structural family of oxide ion conductors, materials important for applications in a variety of electrochemical devices. While some attempts to improve their ionic conductivity have been reported, a detailed understanding of the underlying oxide ion diffusion mechanisms in these materials is still missing. To explore the structure-property relationships leading to the favorable properties, we carried out ab initio molecular dynamics simulations of oxide ion diffusion in CsBi2Ti2NbO10-δ. Our computational study reveals significant out-of-plane dynamics, indicating that the dominant pathway for oxide ion migration is via jumps into and out of the (ab) crystallographic plane. This suggests that further improvement of oxide ion conductivity relative to CsBi2Ti2NbO10-δ could be achieved by enhancing the rotational flexibility of the coordination polyhedra located in the inner perovskite layer, thereby facilitating faster out-of-plane motions.

SYNTHESIS, CHARACTERIZATION, DFT, AND BIOLOGICAL ASSAY OF NEW XANTHATE COMPLEXES WITH NITROGEN BASES

This study introduces a new series of complexes and adducts, denoted by [M(2-PhOEtXant)2.nL], where M represents Mn(II), Fe(II), Co(II), or Ni(II), and the ligand (2-PhOEtXant) is 2-Phenoxyethylxanthate. Varying ligands, including pyridine, piperidine, quinoline, ethylenediamine, and (1,10)-phenanthroline, are explored based on the value of n. Comprehensive characterization, encompassing techniques like 1H-NMR, 13C-NMR, FTIR, AA, CHN analysis, UV-visible spectroscopy, and magnetic property measurements, is employed. Results indicate an octahedral geometry for these complexes, as revealed by effective magnetic moment measurements and electronic spectra analysis. The compounds exhibit noteworthy antioxidant properties, demonstrated through the DPPH radical scavenging method, highlighting their potential as effective antioxidants. Moreover, the complexes display enhanced antibacterial activity against microbial strains compared to free ligands. This research not only delves into the coordination chemistry of these complexes but also underscores their diverse applications. Combining experimental methods with computational insights using Density Functional Theory (DFT) enhances the understanding of dithiolate transition metal complexes. The alignment of computational and experimental outcomes strengthens the reliability of the findings, laying a robust foundation for interdisciplinary exploration. The identified potential applications in optoelectronics, along with the notable antioxidant and antibacterial activities, position these complexes as promising contenders for advanced technologies and scientific applications.

Unlocking the secrets of pressure-driven physical properties of NaNbO3 perovskite-oxide: A computational insight

The current investigation presents the various pressure-induced properties such as structural, elastic, mechanical, optical, and electronic features of NaNbO3 across a pressure range of 0.0–100 GPa. Utilizing the CASTEP tool alongside GGA-PBE based on DFT, comprehensive calculations are conducted. The material displays an indirect energy bandgap, with its magnitude increasing from 1.633 to 2.223 eV under rising pressure. Analysis reveals a covalent character in O–Nb bonds, while O–O and Na–O interactions exhibit an ionic nature. As pressure rises, both lattice parameters and volume exhibit a tendency to decrease. Interestingly, the material exhibits anisotropic behaviour and maintains mechanical stability, transitioning from brittleness at 0.0 GPa to ductility between 10 and 100 GPa. Additionally, it demonstrates superhard characteristics at 0.0–20 GPa and progresses to an ultrahard state from 30 to 100 GPa. Optical properties display a trend of sharpening peaks with a slight shift towards higher energy in the curves. Notably, the material's indirect bandgap renders it suitable for prolonged photocatalysis applications.

Oxidation of Flavin by Molecular Oxygen: Computational Insights into a Possible Radical Mechanism

Oxidation of Flavin by Molecular Oxygen: Computational Insights into a Possible Radical Mechanism

Cycle-to-cycle switching endurance variability in vertically aligned nanocrystalline molybdenum disulfide: computational insights

We propose a model to depict abrupt transient changes in the endurance test results of a resistive switching device comprising vertically oriented layers of nanocrystalline transition metal dichalcogenide layers with respect to the substrate. We aim to relate and understand the so-called resistance drift occurring in the endurance test results with our model, which is further tested using density functional theory simulations. We conclude that the relationship between resistance drift and skin effect is dominated by alternating electric current resistance and surface resistance. These results are crucial for understanding the resistance drift occurring in several resistive switching devices operating based on defects and ions.

Computational Insight into the Physical Properties of Bulk MP (M = Li, Na, K) for Energy Applications.

In this study, we applied density functional theory to compute the electronic, optical, and thermal properties of MP (M = Li, Na, K). We find that the materials under consideration are stable, owing to the lack of negative frequencies in the phonon spectra. LiP exhibits an indirect band gap of 1.43 eV. NaP and KP have direct band gaps of 1.67 and 1.76 eV, respectively. The family of these composites shows strong absorption, observed by their very sharp absorption edges and confirmed by their direct transition from the valence to conduction band. They exhibit strong absorption below 4.0 eV in the optical spectra, which could serve in a solar cell device. The thermal calculations show high zT values of 0.74, 0.78, and 0.64 at 300 K for LiP, NaP, and KP, respectively. Thus, our results could be promising for electronic and thermal devices.

Exploring Novel Antimalarial Compounds Targeting Plasmodium falciparum Enoyl-ACP Reductase: Computational and Experimental Insights.

Malaria, caused by Plasmodium protozoa with Plasmodium falciparum as the most virulent species, continues to pose significant health challenges. Despite the availability of effective antimalarial drugs, the emergence of resistance has heightened the urgency for developing novel therapeutic compounds. In this study, we investigated the enoyl-ACP reductase enzyme of P. falciparum (PfENR) as a promising target for antimalarial drug discovery. Through a comprehensive analysis, we conducted a comparative evaluation of two lead compounds, LD1 (CID: 44405336, lead compounds 1) and LD2 (CID: 72703246, lead compounds 2), obtained from the PubChem/NCBI ligand database, to serve as reference molecules in the identification of potential derivatives using virtual screening assays. Among the newly identified candidates, Ligand 1 (LG1) and Ligand 2 (LG2) exhibited intriguing characteristics and underwent further investigation through docking and molecular dynamics simulations. Ligand 1 (LG1) demonstrated interactions similar to LD1, including hydrogen bonding with Asp218, while Ligand 2 (LG2) displayed superior binding energy comparable to LD1 and LD2, despite lacking hydrogen bonding interactions observed in the control compounds triclosan and its derivative 7-(4-chloro-2-hydroxyphenoxy)-4-methyl-2H-chromen-2-one (CHJ). Following computational validation using the MM/GBSA method to estimate binding free energy, commercially acquired LG1 and LG2 ligands were subjected to in vitro testing. Inhibition assays were performed to evaluate their potential as PfENR inhibitors alongside triclosan as a control compound. LG1 exhibited no inhibitory effects, while LG2 demonstrated inhibitory effects like triclosan. In conclusion, this study contributes valuable insights into developing novel antimalarial drugs by identifying LG2 as a potential ligand and employing a comprehensive approach integrating computational and experimental methodologies.

An Overview of SARS-CoV-2 Potential Targets, Inhibitors, and Computational Insights to Enrich the Promising Treatment Strategies.

The rapid spread of the SARS-CoV-2 virus has emphasized the urgent need for effective therapies to combat COVID-19. Investigating the potential targets, inhibitors, and in silico approaches pertinent to COVID-19 are of utmost need to develop novel therapeutic agents and reprofiling of existing FDA-approved drugs. This article reviews the viral enzymes and their counter receptors involved in the entry of SARS-CoV-2 into host cells, replication of genomic RNA, and controlling the host cell physiology. In addition, the study provides an overview of the computational techniques such as docking simulations, molecular dynamics, QSAR modeling, and homology modeling that have been used to find the FDA-approved drugs and other inhibitors against SARS-CoV-2. Furthermore, a comprehensive overview of virus-based and host-based druggable targets from a structural point of view, together with the reported therapeutic compounds against SARS-CoV-2 have also been presented. The current study offers future perspectives for research in the field of network pharmacology investigating the large unexplored molecular libraries. Overall, the present in-depth review aims to expedite the process of identifying and repurposing drugs for researchers involved in the field of COVID-19 drug discovery.

Comprehensive spectroscopic and computational insight into the binding of vanillin with human transferrin: targeting neuroinflammation in Alzheimer's disease therapeutics.

In present times, vanillin stands out as a promising therapeutic molecule that can be implicated in the treatment of neurodegenerative disorders (NDs), notably Alzheimer's disease (AD). This can be attributed to the highly potent scavenging activity of vanillin against reactive oxygen species (ROS). Oxidative stress leads to generation of ROS that serves a critical role in AD's pathological progression. It is apparent from various studies that diets rich in polyphenols prevent oxidative stress associated with AD development, implying the crucial role of vanillin in AD therapeutics. It is crucial to maintain iron balance to manage AD associated oxidative stress, unveiling the significance of human transferrin (hTf) that maintains iron homeostasis. Here, we have performed an integrated study of spectroscopic and computational approaches to get insight into the binding mechanism of vanillin with hTf. In the preliminary study, molecular docking deciphered that vanillin primarily occupies the hTf binding pocket, forming multiple interactions with its key residues. Moreover, the binding mechanism was evaluated at an atomistic level employing comprehensive molecular dynamic (MD) simulation. MD analysis demonstrated that binding of vanillin to hTf stabilizes its structure, without inducing any significant alterations in its native conformation. The docked complex was maintained throughout the simulations without changing its original conformation. Essential dynamics analysis further confirms that hTf achieved a stable conformation with vanillin. The outcomes were further supplemented by fluorescence spectroscopy which confirms the formation of stable hTf-vanillin complex. Taken together, the current study unveils the interaction mechanism of vanillin with hTf and providing a platform to use vanillin in AD therapeutics in the context of iron homeostasis.

Computational Insights on Structural Sensitivity of Cobalt in NO Electroreduction to Ammonia and Hydroxylamine.

It has been reported that it was selective to produce ammonia on metallic cobalt in the electrocatalytic nitric oxide reduction reaction (eNORR), where hexagonal close-packed (hcp) cobalt outperforms face-centered cubic (fcc) cobalt. However, hydroxylamine is more selectively produced on a cobalt single-atom catalyst (Co-SAC). Herein, we uncover the structural sensitivity over hcp-Co, fcc-Co, and Co-SAC in eNORR by employing a recently developed constant potential simulation method and microkinetic modeling. It was found that the superior activity for ammonia production on hcp-Co can be attributed to its facile electron and proton transfer and a stronger lateral suppression effect from NO* over fcc-Co. The exceptional hydroxylamine selectivity on Co-SAC is due to the modified electronic structure, namely, a positively charged active center. It was found that it is more favorable to produce NOH* over hcp-Co and fcc-Co, while HNO* is more preferable on Co-SAC, which are firmly correlated with the vertical and strong NO adsorption on the former and the moderate adsorption on the latter. In other words, a key factor for selectivity control is the first step of NO* protonation. Therefore, the local structure and electronic structure of the catalysts can be critical in regulating the activity and selectivity in eNORR.