Search

In the present study, ten new substituted 3-hydroxypyridine-4-one derivatives were synthesized in a four-step method, and their chemical structures were confirmed using various spectroscopic techniques. Subsequently, the inhibitory activities of these derivatives against tyrosinase enzyme and their antioxidant activities were evaluated. Amongest the synthesized compounds, 6b bearing a 4-OH-3-OCH3 substitution was found to be a promising tyrosinase inhibitor with an IC50 value of 25.82 μM, which is comparable to the activity of kojic acid as control drug. Kinetic study indicated that compound 6b is a competitive inhibitor of tyrosinase enzyme, which was confirmed by molecular docking results. The molecular docking study and MD simulation showed that compound 6b was properly placed within the tyrosinase binding pocket and interacted with key residues, which is consistent with its biological activity. The DFT analysis demonstrated that compound 6b is kinetically more stable than the other compounds. In addition, compounds 6a and 6b exhibited the best antioxidant activities. The findings indicate that compound 6b could be a promising lead for further studies.

Multi-epitope vaccines strategically tackle rapidly mutating viruses by targeting diverse epitopes from different proteins, providing a comprehensive and adaptable immune protection approach for enhanced coverage against various viral variants. This research employs a comprehensive approach that includes the mapping of immune cells activating epitopes derived from the six structural glycoproteins (A29L, A30L, A35R, L1R, M1R, and E8L) of Monkeypox virus (Mpox). A total of 7 T-cells-specific epitopes, 13 B-cells-specific epitopes, and 5 IFN-γ activating epitopes were forecasted within these glycoproteins. The selection process focused on epitopes indicating high immunogenicity and favorable binding affinity with multiple MHC alleles. Following this, a vaccine has been formulated by incorporating the chosen epitopes, alongside adjuvants (PADRE peptide) and various linkers (EAAAK, GPGPG, and AAY). The physicochemical properties and 3D structure of the multi-epitope hybrid vaccine were analysed for characterization. MD simulations were employed to predict the binding stability between the vaccine and various pathogen recognition receptors such as TLRs (TLR1, TLR2, TLR4, and TLR6), as well as both class I and II MHC, achieved through hydrogen bonding and hydrophobic interactions. Through in silico cloning and immune simulation, it was observed that the multi-epitopes vaccine induced a robust memory immune response upon booster doses, forecasting protective immunity upon viral challenge. This protective immunity was characterized by the production of IgM + IgG antibodies, along with release of inflammatory cytokines like IFN-γ, and IL12, and the activation of various immune cells. This study offers valuable insights into the potential of a multi-epitope vaccine targeting the Mpox virus.

The present study employed a comprehensive approach of network pharmacology, molecular dynamic simulation and in-vitro assays to investigate the underlying mechanism of the anti-osteoarthritic potential of Vanda tessellata extract (VTE). Thirteen active compounds of VTE were retrieved from the literature and the IMPPAT database. All of these passed the drug likeness and oral bioavailability parameters. A total of 535 VTE targets and 2577 osteoarthritis related targets were obtained. The compound-target-disease network analysis revealed vanillin, daucosterol, gigantol and syringaldehyde as the core key components. Protein-protein interaction analysis revealed BCL2, FGF2, ICAM 1, MAPK1, MMP1, MMP2, MMP9, COX2, STAT3 and ESR1 as the hub genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed AGE-RAGE signalling pathway, HIF-1 signalling pathway and ESR signalling pathway as the major signalling pathway of VTE involved in treating osteoarthritis. Molecular docking analysis showed daucosterol and gigantol to have good binding affinity with BCL2, ESR1 and MMP9, and the results were further confirmed through molecular dynamics simulation analysis. The mechanism predicted by network pharmacology was validated in vitro on IL-1β-induced SW982 synovial cells. VTE did not show any cytotoxicity and inhibited the migration of SW982 cells. VTE inhibited the expression level of IL-6, IL-8, TNF-α, PGE-2, MMP-2 and MMP-9 in a dose-dependent manner. VTE inhibited nuclear translocation of NF- κβ and suppressed phosphorylation of p38, extracellular signal-regulated kinase (ERK), and c-Jun NH2-terminal kinase (JNK) of the mitogen-activated protein kinase (MAPK) signalling pathway. The results showed that VTE exerted an anti-osteoarthritic effect by a multi-target, multi-component and multi-signalling pathway approach.

Trans-activation response (TAR) RNA-binding protein (TRBP) has emerged as a key player in the RNA interference pathway, wherein it binds to different pre-microRNAs (miRNAs) and small interfering RNAs (siRNAs), each varying in sequence and/or structure. We hypothesize that TRBP displays dynamic adaptability to accommodate heterogeneity in target RNA structures. Thus, it is crucial to ascertain the role of intrinsic and RNA-induced protein dynamics in RNA recognition and binding. We have previously elucidated the role of intrinsic and RNA-induced conformational exchange in the double-stranded RNA-binding domain 1 (dsRBD1) of TRBP in shape-dependent RNA recognition. The current study delves into the intrinsic and RNA-induced conformational dynamics of the TRBP-dsRBD2 and then compares it with the dsRBD1 study carried out previously. Remarkably, the two domains exhibit differential binding affinity to a 12-bp dsRNA owing to the presence of critical residues and structural plasticity. Furthermore, we report that dsRBD2 depicts constrained conformational plasticity when compared to dsRBD1. Although, in the presence of RNA, dsRBD2 undergoes induced conformational exchange within the designated RNA-binding regions and other residues, the amplitude of the motions remains modest when compared to those observed in dsRBD1. We propose a dynamics-driven model of the two tandem domains of TRBP, substantiating their contributions to the versatility of dsRNA recognition and binding.

The spread of drug-resistant tuberculosis strains has become a significant economic burden globally. To tackle this challenge, there is a need to develop new drugs that target specific mycobacterial enzymes. Among these enzymes, InhA, which is crucial for the survival of Mycobacterium tuberculosis, is a key target for drug development. Herein, 24 compounds were synthesized by merging 4-carboxyquinoline with triazole motifs. These molecules were then tested for their effectiveness against different strains of tuberculosis, including M. bovis BCG, M. tuberculosis, and M. abscessus. Additionally, their ability to inhibit the InhA enzyme was also evaluated. Several molecules showed potential as inhibitors of M. tuberculosis. Compound 5n displayed the highest efficacy with a MIC value of 12.5 μg/mL. Compounds 5g, 5i, and 5n exhibited inhibitory effects on InhA. Notably, 5n showed significant activity compared to the reference drug Isoniazid. Molecular docking analysis revealed interactions between these molecules and their target enzyme. Additionally, the molecular dynamic simulations confirmed the stability of the complexes formed by quinoline-triazole conjugate 5n with the InhA. Finally, 5n underwent in silico analysis to predict its ADME characteristics. These findings provide promising insights for developing novel small compounds that are safe and effective for the global fight against tuberculosis.

The NOD-Like Receptor Protein-3 (NLRP3) inflammasome is a key therapeutic target for the treatment of epilepsy and has been reported to regulate inflammation in several neurological diseases. In this study, a machine learning-based virtual screening strategy has investigated candidate active compounds that inhibit the NLRP3 inflammasome. As machine learning-based virtual screening has the potential to accurately predict protein-ligand binding and reduce false positives outcomes compared to traditional virtual screening. Briefly, classification models were created using Support Vector Machine (SVM), Random Forest (RF), and K-Nearest Neighbor (KNN) machine learning methods. To determine the most crucial features of a molecule's activity, feature selection was carried out. By utilizing 10-fold cross-validation, the created models were analyzed. Among the generated models, the RF model obtained the best results as compared to others. Therefore, the RF model was used as a screening tool against the large chemical databases. Molecular operating environment (MOE) and PyRx software's were applied for molecular docking. Also, using the Amber Tools program, molecular dynamics (MD) simulation of potent inhibitors was carried out. The results showed that the KNN, SVM, and RF accuracy was 0.911 %, 0.906 %, and 0.946 %, respectively. Moreover, the model has shown sensitivity of 0.82 %, 0.78 %, and 0.86 % and specificity of 0.95 %, 0.96 %, and 0.98 % respectively. By applying the model to the ZINC and South African databases, we identified 98 and 39 compounds, respectively, potentially possessing anti-NLRP3 activity. Also, a molecular docking analysis produced ten ZINC and seven South African compounds that has comparable binding affinities to the reference drug. Moreover, MD analysis of the two complexes revealed that the two compounds (ZINC000009601348 and SANC00225) form stable complexes with varying amounts of binding energy. The in-silico studies indicate that both compounds most likely display their inhibitory effect by inhibiting the NLRP3 protein.

Introduction: Multiple sclerosis (MS) is an autoimmune and inflammatory disease that destroys the protective coating of central nervous system (CNS) nerve fibers and affects over 2.8 million people worldwide. Despite several studies on new therapeutic targets and lead compounds, MS disease has limited treatment options. This condition may be caused by a complicated interaction of environmental and genetic variables. Studies showed that MS-associated microglial cells’ increased MAPKERK activity may cause CNS inflammation and oligodendrocyte damage. Thus, screening for lead compounds that inhibit MAPKERK may protect brain cells and slow disease progression.Methods: The study aims to discover compounds that may inhibit MAPKERK as a novel approach for protecting the nervous system in managing MS. The study includes in silico methods, such as virtual screening, molecular docking, Density-functional theory (DFT) investigations (using the B3LYP/6–31++G(d,p) basis set in a gas phase environment), drug likeness scores, and molecular dynamic (MD) simulations.Results and Discussion:During the docking process with the MAPKERK protein, it was shown that the ligand L12 receptor had the best binding affinity, with a docking score of -6.18 kcal/mol. To investigate the stability of the binding, a 100 ns MD simulation was performed on the complex formed by the MAPKERK protein and L12. The receptor-ligand combination exhibited significant stability throughout the duration of the MD simulation. Additionally, the pharmacokinetic and drug-likeness properties of these ligands suggest that they have the potential to be considered viable candidates for future development in MS management.

A new series of cis-dihydroxy-indeno[1,2-d]imidazolone compounds with distinct structures were synthesized to investigate their potential as inhibitors of the Glycogen synthase kinase 3 (GSK-3). The synthesized compounds were thoroughly characterized using IR, Mass, 1H, and 13C NMR, and in silico screening, including molecular docking, DFT studies using the B3LYP/6-31++G(d,p) basis set in the gas phase drug likeness scores, and molecular dynamic simulation studies, was performed to evaluate protein–ligand interactions and determine the stability of the top-ranked conformation. Our results suggested that compound 4 g, among these compounds, has the potential to be a novel GSK-3 inhibitor as an anticancer agent.

Sitagliptin is a medication used to manage type-2 diabetes. The present study investigates the experimental and theoretical results of Sitagliptin (SG). Density functional theory (DFT) calculations were used to determine optimized parameters at the B3LYP functional /6-31++G(d,p) basis set. In addition Time-dependent DFT is used to compute excited states of SG and SG-Ag6 and predict UV spectra. The electronic properties of silver nano cages containing SG have exhibited a notable enhancement. Natural bond orbital (NBO) analysis was also used to determine charge transfer within the molecule and stabilization energy. Electronic properties such as molecular electrostatic potential (MEP), frontier molecular orbital (FMO) analysis of SG and SG-Ag6 were investigated. The chemical significance of SG has been discussed using electron localization function (ELF) and local orbital locator functions (LOL) with contour images. Sitagliptin appears to have promise as a treatment for the chosen inhibitors, according to the docking binding affinities and the formation of a significant amount of hydrogen bonds. The molecular dynamics simulations were also performed using Gromacs 5.1.3 and discussed.

Abstract In this article, the formation of laser-induced graphene on the two natural polymers, cellulose, and lignin, as precursors was investigated with molecular dynamics simulations and some experiments. These eco-friendly polymers provide significant industrial advantages due to their low cost, biodegradability, and recyclable aspects. It was discovered during the simulation that LIG has numerous defects and a porous structure. Carbon monoxide, H2, and water vapor are gases released by cellulose and lignin substrates. H2O and CO are released when the polymer transforms into an amorphous structure. Later on, as the amorphous structure changes into an ordered graphitic structure, H2 is released continuously. Since cellulose monomer has a higher mass proportion of oxygen (49%) than lignin monomer (29%), it emits more CO. The LIG structure contains many 5- and 7-carbon rings, which cause the structure to have bends and undulations that go out of the plane. In addition, to verify the molecular dynamics simulation results with experimental tests, we used a carbon dioxide laser to transform filter paper, as a cellulose material, and coconut shell, as a lignin material, into graphene. Surprisingly, empirical experiments confirmed the simulation results.

Recently, Co–Cr–Ni medium-entropy alloys (MEAs) have garnered significant attention in the materials field owing to exceptional properties. However, the various mechanisms of transformation induced plasticity (TRIP) and twinning induced plasticity (TWIP) effects with variation of chemical compositions, strain rates, temperature and grain size in polycrystalline Co–Cr–Ni MEAs remains challenging. By utilizing molecular dynamics simulations, the uniaxial tensile deformation of polycrystalline Co–Cr–Ni MEAs, including equiatomic CoCrNi, and non-equiatomic Co10(CrNi)90, Cr10(CoNi)90 and Ni10(CoCr)90, has been investigated. The influence of strain rates and deformation temperatures on the mechanical properties and deformation mechanisms of CoCrNi MEA has also been explored under uniaxial tensile loading. Further, dislocation multiplication, slip motion, microstructure evolution, and their interplay with tensile deformation under different conditions have also been studied. Additionally, the relationship between different grain sizes and the flow stress of polycrystalline CoCrNi MEA has also been discussed. The findings reveal that Co10(CrNi)90 MEA exhibits highest yield stress, Young's modulus, and flow stress. While CoCrNi MEA and Cr10(CoNi)90 MEA with equiatomic ratios display similar mechanical properties, Ni10(CoCr)90 MEA demonstrates superior ductility owing to the strong TWIP and TRIP effects. Besides, strain rate, deformation temperature, and grain size all have significant impacts on the deformation mechanisms of polycrystalline CoCrNi MEA.

Following the previous paper focusing on tribological properties of hydrofluoroolefin (HFO) refrigerant, the adsorption behavior of refrigerants on the nascent iron surface was investigated experimentally and the adsorption structure, adsorption energy and dynamic process of chemical reaction of refrigerants were analyzed by a molecular simulation. The adsorption behavior on the nascent iron surface was highly dependent on the molecular structure of the refrigerant. HFO refrigerants with an unsaturated bond exhibited high adsorption activity, and halogen species also affected the adsorption activity. HFO showed higher adsorption activity than organic ester, phosphate ester and alkyl sulfide as model compounds of refrigerator oil. In adsorption simulation by neural network potential (NNP), HFO molecules showed large negative adsorption energy. The mechanism for this stronger adsorption of HFO species, density functional theory calculation was conducted, and it showed that HFO adsorbs on iron surface by electron donation from the molecule and back-donation from iron surface. There was also a good correlation between the experimental adsorption activity and the NNP-obtained adsorption energy. MD simulation of molecule adsorbed on the nascent surface at temperature of 298 K was subsequently done using the iron fluoride has been experimentally detected on friction track by using XPS in the first report of this study. It was concluded that the adsorption and tribochemical formation of iron fluoride from HFO are supported by molecular simulation performed in this study.

The emergence of SARS-CoV-2 created a havoc worldwide, causing high morbidity, serious complications and mortality. The ORF1ab of SARS-CoV-2 has 16 non-structural proteins which are required for genome replication and transcription. All of these are druggable targets, of which NSP12 (RNA-dependent RNA polymerase), was selected as a potential target for drug molecules. Remdesivir is a recommended drug for SARS-CoV-2 and it targets the RdRp protein. Although Remdesivir was given to COVID-19 patients based on their clinical manifestations, yet the transmission and spread of the virus continued and to add to its pandemicity, new variants emerged from time to time. This necessitates the need for molecular modification of existing antiviral drugs so that more precise targets for halting viral replication can be selected. For this, the approach used was repurposing of the existing drugs. In the present study, ten FDA-approved drugs were chosen on the basis of their properties of inhibiting the RdRp protein. These drugs were subjected for checking the docking score with the target protein. Of these, Remdesivir, Ribavirin, Favipiravir and Baloxavir were taken for further analysis on the basis of their best scores. These drugs were then modified to check the efficiency to inhibit the RdRp and to stop the replication rate of the virus. We docked the modified drugs with the macrodomain of RdRp by using the CB-Dock web server and checked the binding affinity and amino acid contact residues. The modified drugs were also checked for bioactivity in the Molinspiration cheminformatics online tool. Our results showed increased affinity for RdRp of SARS-CoV-2 when compared to the original compound. We also checked the synthetic accessibility of the drugs using the SwissADME tool. The study showed promising results when modified. The findings reported need further confirmation through wet lab studies.

N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC), a quaternized chitosan derivative, has been shown to exhibit a broad spectrum of antimicrobial activity, especially against bacteria and enveloped viruses. Despite this, molecular docking studies showing its atomic-level mechanisms against these microorganisms are scarce. Here, for the first time, we employed molecular docking analyses to investigate the potential antibacterial activity of HTCC against Staphylococcus aureus and its antiviral activity against human immunodeficiency virus 1 (HIV-1). According to the findings, HTCC exhibited promising antibacterial activity with high binding affinities; however, it had limited antiviral activity. To validate these theoretical outcomes, experimental studies were conducted. Different derivatives of HTCC were synthesized and characterized using NMR, XRD, FTIR, and DLS. The in vitro assays validated the potent antibacterial efficacy of HTCC against S. aureus, whereas the antiviral studies did not show good antiviral activity. However, our research also revealed a promising avenue for further exploration of the antimicrobial activity of HTCC nanoparticles (NPs), since, thus far, no studies have been conducted to show the antiviral activity of HTCC NPs against HIV-1. The nanosized HTCC exhibited superior antiviral performance compared to the parent polymers, with complete (100%) inhibition of HIV-1 viral activity at the highest tested concentration (0.33 mg/mL).

Staphylococcus aureus infections present a significant threat to the global healthcare system. The increasing resistance to existing antibiotics and their limited efficacy underscores the urgent need to identify new antibacterial agents with low toxicity to effectively combat various S. aureus infections. Hence, in this study, we have screened T-muurolol for possible interactions with several S. aureus-specific bacterial proteins to establish its potential as an alternative antibacterial agent. Based on its binding affinity and interactions with amino acids, T-muurolol was identified as a potential inhibitor of S. aureus lipase, dihydrofolate reductase, penicillin-binding protein 2a, D-Ala:D-Ala ligase, and ribosome protection proteins tetracycline resistance determinant (RPP TetM), which indicates its potentiality against S. aureus and its multi-drug-resistant strains. Also, T-muurolol exhibited good antioxidant and anti-inflammatory activity by showing strong binding interactions with flavin adenine dinucleotide (FAD)-dependent nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase, and cyclooxygenase-2. Consequently, molecular dynamics (MD) simulation and recalculating binding free energies elucidated its binding interaction stability with targeted proteins. Furthermore, quantum chemical structure analysis based on density functional theory (DFT) depicted a higher energy gap between the highest occupied molecular orbital and lowest unoccupied molecular orbital (EHOMO-LUMO) with a lower chemical potential index, and moderate electrophilicity suggests its chemical hardness and stability and less polarizability and reactivity. Additionally, pharmacological parameters based on ADMET, Lipinski’s rules, and bioactivity score validated it as a promising drug candidate with high activity toward ion channel modulators, nuclear receptor ligands, and enzyme inhibitors. In conclusion, the current findings suggest T-muurolol as a promising alternative antibacterial agent that might be a potential phytochemical-based drug against S. aureus. This study also suggests further clinical research before human application.

In this article, the formation of laser-induced graphene on the two natural polymers, cellulose, and lignin, as precursors was investigated with molecular dynamics simulations and some experiments. These eco-friendly polymers provide significant industrial advantages due to their low cost, biodegradability, and recyclable aspects. It was discovered during the simulation that LIG has numerous defects and a porous structure. Carbon monoxide, H2, and water vapor are gases released by cellulose and lignin substrates. H2O and CO are released when the polymer transforms into an amorphous structure. Later on, as the amorphous structure changes into an ordered graphitic structure, H2 is released continuously. Since cellulose monomer has a higher mass proportion of oxygen (49%) than lignin monomer (29%), it emits more CO. The LIG structure contains many 5- and 7-carbon rings, which cause the structure to have bends and undulations that go out of the plane. In addition, to verify the molecular dynamics simulation results with experimental tests, we used a carbon dioxide laser to transform filter paper, as a cellulose material, and coconut shell, as a lignin material, into graphene. Surprisingly, empirical experiments confirmed the simulation results. [ABSTRACT FROM AUTHOR]

Azobenzene-incorporated liquid crystalline polymer (azo-LCP), which undergo property change and deformation upon Ultra violet and visible light stimulation, are promising materials in various fields. This study investigated the effect of azobenzene concentration on photosoftening based on the photoisomerization of an azo-LCP. The experimental results confirmed that as the azobenzene concentration increased, the order parameter decreased and mechanical properties deteriorated. Photoisomerization and photosoftening was also conducted on an azo-LCP unit cell constructed by molecular dynamics simulation. The simulation results showed that changes in the order parameter, length contraction and elastic modulus due to the photosoftening, in alignment with the experimental results. [ABSTRACT FROM AUTHOR]

Salvurmin A and Salvurmin B are novel cytotoxic ursane triterpenoids isolated from Salvia urmiensis, an endemic plant species of Iran. The isolation, structure elucidation and in vitro anticancer properties of these two compounds were reported in our recent publications. For further studies, we assessed computational studies of Salvurmin A and Salvurmin B as anticancer agents. Molecular docking studies were performed to predict their affinity toward VEGFR-2 and Bcl-2 apoptosis regulator. Molecular dynamic simulation was also performed on the potent compound (Salvurmin B) to understand the virtual interaction in the active site of the enzyme (VEGFR-2). In addition, to obtain details of the structural properties of the compounds DFT analysis was performed. In order to better comprehend the reactivity of these molecules, the frontier orbitals were studied in detail, including HOMO–LUMO gap, molecular softness and hardness, electron affinity, chemical potential and electron surface potential studies. Taken together, Salvurmin B had desired chemical reactivity compared to Salvurmin A. In silico ADMET profiling calculations were also performed. Therefore, computational studies of the compounds in this study confirmed in vitro anticancer assessment in our recent report, and Salvurmin B can be considered as a potential candidate for further studies against human carcinoma cells. [ABSTRACT FROM AUTHOR]

TMPRSS6 (transmembrane protease, serine 6) plays an important role in the cleavage of hemojuvelin (HJV), a key protein involved in the regulation of hepcidin metabolism. TMPRSS6 cleaves HJV at specific sites, leading to the activation of the bone morphogenetic protein (BMP6-SMAD) pathway. This pathway further leads to the production of hepcidin (a liver peptide enzyme), which promotes iron absorption and removal from the bloodstream. In-silico pharmacophore analysis is used in this study to identify potential small therapeutic compounds that inhibit TMPRSS6 activity. Pharmacophore investigations of known inhibitors (peptidomimetic benzothiazole) were carried out to identify the molecules' important properties for interacting with the target. The pharmacophore model of the TMPRSS6 (PDB ID: 6N4T) inhibitor (KD7) pharmacophore features were used to screen the small molecules library that binds to the target and modulates its activity. The docking parameters of the top 5 hit molecules had lower binding energy in comparative analysis to reference molecule. The best-fit pharmacophore feature ligands were docked at the binding site of the target protein. This study demonstrates that knocking out the enzyme reduces the effects of iron overload in conditions like hemochromatosis and beta-thalassemia. In-silico investigation discovered significant evidence of catalytic activity. [ABSTRACT FROM AUTHOR]

Citrus essential oils (EOs) contain a variety of secondary metabolites, including coumarins (Cs), furocoumarins (FCs) and polymethoxyflavones (PMFs), all with different biological activities. While Regulation (EC) No 1334/2008 strictly regulates the use of coumarins, undesirable side effects of consuming furocoumarins remain without established maximum toxicity limits for human dietary intake. This study is based on an in‐silico approach aimed at determining these toxicity limits for the oxygenated heterocyclic compounds of citrus EOs approved for use in food. In addition, an innovative quantitative structure‐property relationship (QSPR) using the linear retention index system was explored to characterize the oxygenated heterocyclic compounds (COHs) present in these essential oils. Molecular docking of the studied compounds provided crucial insights into the structure‐odor relationships, offering insights into their mechanisms of action. In addition, an analysis of the pharmacokinetic and pharmacodynamic properties through ADME‐Tox deconstruction provides insight into the potential side effects of their consumption. The results are consolidated by dynamic simulations, providing crucial data for the development of regulations on the maximum toxicity limits of citrus EOs, given the health implications of the various compounds such as coumarins, furocoumarins and polymethoxyflavones present in these essential oils. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic caused unprecedented damage to humanity, and while vaccines have been developed, they are not fully effective against the SARS-CoV-2 virus. Limited targeted drugs, such as Remdesivir and Paxlovid, are available against the virus. Hence, there is an urgent need to explore and develop new drugs to combat COVID-19. This study focuses on exploring microbial natural products from soil-isolated bacteria Streptomyces sp. strain 196 and RI.24 as a potential source of new targeted drugs against SARS-CoV-2. Molecular docking studies were performed on holoRdRp and nsp13, two key factors responsible for virus replication factor. Our in silico studies, K-252-C aglycone indolocarbazole alkaloid (K252C) and daunorubicin were found to have better binding affinities than the respective control drugs, with K252C exhibiting binding energy of − 9.1 kcal/mol with holoRdRp and − 9.2 kcal/mol with nsp13, and daunorubicin showing binding energy at − 8.1 kcal/mol with holoRdRp and − 9.3 kcal/mol with nsp13. ADMET analysis, MD simulation, and MM/GBSA studies indicated that K252C and daunorubicin have the potential to be developed as targeted drugs against SARS-CoV-2. The study concludes that K252C and daunorubicin are potential lead compounds that might suppress the inhibition of SARS-CoV-2 replication among the tested microbial compounds and could be developed as targeted drugs against COVID-19. In the future, further in vitro studies are required to validate these findings. [ABSTRACT FROM AUTHOR]

Breast cancer begins in the breast cells, mainly impacting women. It starts in the cells that line the milk ducts or lobules responsible for producing milk and can spread to nearby tissues and other body parts. In 2020, around 2.3 million women across the globe received a diagnosis, with an estimated 685,000 deaths. Additionally, 7.8 million women were living with breast cancer, making it the fifth leading cause of cancer-related deaths among women. The mutational changes, overexpression of drug efflux pumps, activation of alternative signalling pathways, tumour microenvironment, and cancer stem cells are causing higher levels of drug resistance, and one of the major solutions is to identify multitargeted drugs. In our research, we conducted a comprehensive screening using HTVS, SP, and XP, followed by an MM/GBSA computation of human-approved drugs targeting HER2/neu, BRCA1, PIK3CA, and ESR1. Our analysis pinpointed IRESSA (Gefitinib-DB00317) as a multitargeted inhibitor for these proteins, revealing docking scores ranging from −4.527 to −8.809 Kcal/mol and MM/GBSA scores between −49.09 and −61.74 Kcal/mol. We selected interacting residues as fingerprints, pinpointing 8LEU, 6VAL, 6LYS, 6ASN, 5ILE, and 5GLU as the most prevalent in interactions. Subsequently, we analysed the ADMET properties and compared them with the standard values of QikProp. We extended our study for DFT computations with Jaguar and plotted the electrostatic potential, HOMO and LUMO regions, and electron density, followed by a molecular dynamics simulation for 100 ns in water, showing an utterly stable performance, making it a suitable drug candidate. IRESSA is FDA-approved for lung cancer, which shares some pathways with breast cancers, clearing the hurdles of multitargeted drugs against breast and lung cancer. This has the potential to be groundbreaking; however, more studies are needed to concreate IRESSA's role. [ABSTRACT FROM AUTHOR]

Quantum computing in biology is one of the most rapidly evolving fields of technology. Protein folding is one of the key challenges which requires accurate and efficient algorithms with a quick computational time. Structural conformations of proteins with disordered regions need colossal amount of computational resource to map its least energy conformation state. In this regard, quantum algorithms like variational quantum eigensolver (VQE) are applied in the current research work to predict the lowest energy value of 50 peptides of seven amino acids each. VQE is initially used to calculate the energy values over which variational quantum optimization is applied via conditional value at risk (CVaR) over 100 iterations of 500,000 shots each to obtain least ground-state energy value. This is compared to the molecular dynamics-based simulations of 50 ns each to calculate the energy values along with the folding pattern. The results suggest efficient folding outcomes from CVaR-VQE compared to MD-based simulations and HMM-SA. With the ever-expanding quantum hardware and improving algorithms, the problem of protein folding can be resolved to obtain in-depth insights on the biological process and drug design. [ABSTRACT FROM AUTHOR]

Coleus forskohlii (Willd.) Briq. is a medicinal herb of the Lamiaceae family. It is native to India and widely present in the tropical and sub-tropical regions of Egypt, China, Ethiopia, and Pakistan. The roots of C. forskohlii are edible, rich with pharmaceutically bioactive compounds, and traditionally reported to treat a variety of diseases, including inflammation, respiratory disorders, obesity, and viral ailments. Notably, the emergence of viral diseases is expected to quickly spread; consequently, these data impose a need for various approaches to develop broad active therapeutics for utilization in the management of future viral infectious outbreaks. In this study, the naturally occurring labdane diterpenoid derivative, Forskolin, was obtained from Coleus forskohlii. Additionally, we evaluated the antiviral potential of Forskolin towards three viruses, namely the herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), hepatitis A virus (HAV), and coxsackievirus B4 (COX-B4). We observed that Forskolin displayed antiviral activity against HAV, COX-B4, HSV-1, and HSV-2 with IC50 values of 62.9, 73.1, 99.0, and 106.0 μg/mL, respectively. Furthermore, we explored the Forskolin's potential antiviral target using PharmMapper, a pharmacophore-based virtual screening platform. Forskolin's modeled structure was analyzed to identify potential protein targets linked to its antiviral activity, with results ranked based on Fit scores. Cathepsin L (PDB ID: 3BC3) emerged as a top-scoring hit, prompting further exploration through molecular docking and MD simulations. Our analysis revealed that Forskolin's binding mode within Cathepsin L's active site, characterized by stable hydrogen bonding and hydrophobic interactions, mirrors that of a co-crystallized inhibitor. These findings, supported by consistent RMSD profiles and similar binding free energies, suggest Forskolin's potential in inhibiting Cathepsin L, highlighting its promise as an antiviral agent. [ABSTRACT FROM AUTHOR]

This study aimed to examine the influence of Caffeic Acid on the structural, functional, and thermal stability characteristics of lysozyme (LYZ), a critical enzyme that plays a vital role in the immune system. Initially, the Caffeic Acid-LYZ binding interaction was scrutinized through a combination of spectroscopic techniques: UV–Vis's absorption spectra, circular dichroism (CD), and fluorescence spectroscopy. The UV–Vis absorption spectra analysis indicated an augmentation in the absorption of LYZ at 280 nm upon exposure to Caffeic Acid. Additionally, the findings from fluorescence spectroscopy pointed toward the formation of a ground-state complex, as deduced from the static quenching of LYZ fluorescence. Based on the thermodynamic analysis, it was found that the binding process exhibited spontaneity, and the predominant stabilizing forces for the complex were found to be hydrogen bonds and van der Waals forces. The kinetic experiment also demonstrated that the LYZ's activity was reduced consequently to the addition of Caffeic Acid. Further, the CD values showed the conformational changes in the enzyme during complexation. The complementary computational approaches corroborated the empirical results derived from spectroscopic investigations. Molecular docking predicted the most favorable binding site for Caffeic Acid on LYZ, while molecular dynamics simulations confirmed the stability of the resulting complex. [ABSTRACT FROM AUTHOR]

In this study, the elastic mechanical properties of heat deflection temperature (HDT) of a polymeric matrix composite reinforced with silica particles have been studied at the atomic scale by the molecular dynamics simulation method. Ten atomic samples including pure PLA and 9 nanocomposites with 1, 2, and 3% of volume fractions of silica nanoparticles with different atomic radii of 20, 30, and 50 Å, were constructed. The Young's modulus of these samples has been calculated after equilibrium and applying the NVT ensemble. Moreover, the variations of Young's modulus with temperature were measured for different atomic models and the HDT for the nanocomposites were extracted. The results of the simulations showed that the sample with a 20 Å radius of nanoparticle and volume fraction of 3% had the largest Young's modulus compared to other samples. In this sample, Young's modulus has reached 5193 MPa, which has shown a 238% increase compared to the pure polymer. Also, the value of the HDT in this sample was calculated about modulus 119 C° about 133% higher than pure polymer. The obtained values of Young's modulus and HDT for pure polymer showed a good agreement with the experimental results. [ABSTRACT FROM AUTHOR]

In Parallel programming, a programmer needs to understand hardware environment, programming paradigm and primitives available in the programming language. Most of the time, parallel programmes are written for a specific architecture and cannot typically adapt to other architectures Particularly, programs written for shared memory architectures are unsuitable for distributed or hybrid architectures. This paper proposes Adaptive Design Pattern for Parallel Programming to improve adaptability, flexibility with achieving performance on different architectures. Molecular Dynamics (MD) simulation is required to scale to various architectures from simple machine to cluster of workstations. In this study, MD Simulation experimented using both pure benchmark code and code based on adaptive design patterns. Redesigned MD Simulation with Adaptive Design Pattern claims parallel efficiency from 56% to 90% for different number of processing elements used. The solution demonstrates adaptability to different architectures and scalability to use with large number of atoms and long duration simulation. [ABSTRACT FROM AUTHOR]

A thymol-based molecule was synthesized and characterized. The anti-proliferative activity of molecule 4 was tested in vitro in three cancer cell lines and a healthy human cell line. The results showed that this molecule had cytotoxic effects on the human cell lines studied. Images of the cells were taken using the Leica inverted microscope. Molecular docking, molecular dynamics simulation, density functional theory calculations, and computational pharmacokinetics analysis of molecule 4 were carried out. The binding mode of the molecule with ABL1 was revealed through molecular docking. The stability of the complexes procured from the docking was assessed through molecular dynamics simulation. The computational analysis revealed that the antiproliferative effect of molecule 4 on the cancer cell lines might result from its potential to inhibit ABL1. In addition, molecule 4 was found to have ideal pharmacokinetic properties to be used as a drug candidate molecule. Hence, the experimental and computational studies indicated its derivatives might have promising antiproliferative activity. [ABSTRACT FROM AUTHOR]

Context: Mycobacterial membrane proteins Large 3 (MmpL3) is responsible for the transport of mycobacterial acids out of cell membrane to form cell wall, which is essential for the survival of Mycobacterium tuberculosis (Mtb) and has become a potent anti-tuberculosis target. SQ109 is an ethambutol (EMB) analogue, as a novel anti-tuberculosis drug, can effectively inhibit MmpL3, and has completed phase 2b-3 clinical trials. Drug resistance has always been the bottleneck problem in clinical treatment of tuberculosis. The S288T mutant of MmpL3 shows significant resistance to the inhibitor SQ109, while the specific action mechanism remains unclear. The results show that MmpL3 S288T mutation causes local conformational change with little effect on the global structure. With MmpL3 bound by SQ109 inhibitor, the distance between D710 and R715 increases resulting in H-bond destruction, but their interactions and proton transfer function are still restored. In addition, the rotation of Y44 in the S288T mutant leads to an obvious bend in the periplasmic domain channel and an increased number of contact residues, reducing substrate transport efficiency. This work not only provides a possible dual drug resistance mechanism of MmpL3 S288T mutant but also aids the development of novel anti-tuberculosis inhibitors. Methods: In this work, molecular dynamics (MD) and quantum mechanics (QM) simulations both were performed to compare inhibitor (i.e., SQ109) recognition, motion characteristics, and H-bond energy change of MmpL3 after S288T mutation. In addition, the WT_SQ109 complex structure was obtained by molecular docking program (Autodock 4.2); Molecular Mechanics/ Poisson Boltzmann Surface Area (MM-PBSA) and Solvated Interaction Energy (SIE) methods were used to calculate the binding free energies (∆Gbind); Geometric criteria were used to analyze the changes of hydrogen bond networks. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a complex neurodegenerative disease with a limited number of therapeutic options. β-Secretase 1 (BACE1) is a key enzyme involved in the production of amyloid beta peptides, which are central to AD pathology. Targeting BACE1 has emerged as a promising strategy for the treatment of AD. Therefore, the present study aimed to discover novel drug candidates from cyanobacteria for the treatment of AD through in silico research. In this study, Schrödinger tools were used to study the binding affinities and interactions of cyanobacteria metabolites with BACE1. Almost 120 cyanobacteria metabolites against BACE1 were used for the computational investigation. Ultimately, four marine-derived compounds, namely lyngbyastatin 7, homodolastin 3, lyngbyabellin E1, and symplostatin analogue 4, showed strong binding affinities to the active site of BACE1, forming crucial hydrogen bonds and hydrophobic interactions. The binding energy values of these compounds suggest their potential as BACE1 inhibitors. Furthermore, molecular dynamics simulations confirmed the stability of these ligand-protein complexes over a period of 25 ​ns? Our results provide valuable insights into the potential of lyngbyastatin 7, homodolastin 3, lyngbyabellin E1, and symplostatin analog 4 as effective drugs for inhibiting BACE1. These marine-derived compounds are promising for further in vitro and in vivo studies. The present research suggests that these molecules could offer new avenues for the development of novel therapeutics for the treatment of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Background: About 0.7-1.0 million people worldwide have been suffering from Leishmaniasis. It falls under a neglected tropical disease (NTD) and is transmitted by biting infected female phlebotomine sandflies. The implication of "the NTD road map: together towards 2030" in the infection-prone regions worldwide has curtailed morbidity to a greater extent. However, limited options in antileishmanial oral and topical drugs must decipher more therapeutically efficacious agents to cure and eradicate the disease. Methods: Virtual screening based on structure, docking, & molecular dynamics approaches were adopted to identify potential lead molecules against UvrD-like helicase of Leishmania donovani from the MCULE database. Lipinski rule of five, N/O atoms (1-15), number of rings (1-2), HBDs (4-5), and HBAs (5-10) were applied as initial filters of SBVS. AutoDock Vina and GROMACS packages were used for docking and MD simulations, respectively. Results: Initial filters of SBVS workflow yielded 93885 ligand hits out of 100 plus million investigational ligands. Following the toxicology test, 28 ligands were gotten that were additional reduced to molecules (17) when accepted done the BOILED Egg model of the ADME. Six molecules were shortlisted with zero violation compliance of drug-likeness further than Lipinski RO5 viz., Egan, Veber, Muegge, Ghose, & bioavailability score having ΔG (-6.7 to -7.4 kcalmol-1) lesser than reference inhibitor miltefosine (-4.9 kcalmol-1). The stability of MCULE-5754880195-0-2 was found to be greater than the known inhibitor and ligand molecules mentioned above. Conclusion: MCULE-5754880195-0-2 has all therapeutic features by way of an admirable oral drug molecule & could be encouraging in Leishmaniasis prevention & treatment. [ABSTRACT FROM AUTHOR]

The density functional theory (DFT), a well-known tool, can be employed to predict the high electron density position and HOMO–LOMO difference in energy in the inhibitor structure which has a high probability of donating electrons to the metal surface. Fukui functions are connected to the Frontier orbital theory (also known as the Fukui theory of reactivity and selection) and describe how nucleophiles target the highest occupied orbital (HOMO) while depositing their excess electrons in the lowest unoccupied orbital (LUMO). However, it is insufficient for predicting the corrosion inhibition mechanism occurring on the metal surface, such as the adsorption position of the inhibitor on the metal surface to form an adsorption layer. Hence, molecular dynamic (MD) simulation is a reliable method to better understand the interaction and adsorption behaviour of an inhibitor on the metal surface. MD was explored in the phase-related adsorption of the solution. The RDF can be used to identify the average interaction distance along with the number of metal atoms that are within a particular distance of the inhibitor molecule. It can be used to identify the type of adsorption. Hence, this review is focused on the compilation and brief elaboration of the DFT, Fukui indices, MD simulation, and RDF findings for the corrosion inhibition mechanisms. [ABSTRACT FROM AUTHOR]

Over the past century, chemicals and energy have increasingly been derived from non-renewable resources. The growing demand for essential chemicals and shrinking inventory make reliable, sustainable sources essential. Carbohydrates offer by far the greatest carbon supply. Furan compounds, a particular family of dehydration products, are believed to offer high chemical potential. Here, we analyze 5-HMF (5, hydroxymethylfurfural) and some of its derivatives in particular, a furan-type platform chemical. To analyze the therapeutic potential of HMF and its derivatives, this study utilized cutting-edge technologies such as computer-aided drug design, virtual screening, molecular docking, and molecular dynamic simulation. We conducted 189 docking simulations and examined some of the most promising dock poses using the molecular dynamic simulator. As for the receptors for our compounds, the leading candidates are human acetylcholinesterase, beta-lactamases, P. aeruginosa LasR, and S. aureus tyrosyl-tRNA synthetases. Out of all derivatives considered in this study, 2,5-furandicarboxylic acid (FCA) performed best. [ABSTRACT FROM AUTHOR]

Shear-coupled grain boundary motion (SCGBM) is an important and efficacious plasticity mechanism in the deformation of metals. In this work, a molecular dynamic (MD) simulation of the interaction between the SCGBM of Σ9[110](221) GB and Cu-rich precipitates in α-iron was carried out. The effects of the size, the temperature, and the composition of the Cu precipitates were also studied. It was found that the precipitates inhibited the GB motion significantly, and the configuration transformation from spheroid to ellipsoid was also investigated in the simulation results. The critical stress of the interaction increased with the size of the precipitates. At higher temperatures, the GB sliding event increased the critical stress of the GB motion, which was higher than that of the interaction, inducing no stress-rise stage in the stress–time curve. The critical stress of the CuNi precipitates on the SCGBM was higher than that of the pure Cu precipitates with the same size, which was one of the reasons for the outstanding strength of the high-strength low-alloy (HSLA) steels compared with the traditional Cu-containing steels. [ABSTRACT FROM AUTHOR]

SARS-CoV-2, also referred to as severe acute respiratory syndrome coronavirus 2, is the virus responsible for causing COVID-19, an infectious disease that emerged in Wuhan, China, in December 2019. Among its crucial functions, NSP6 plays a vital role in evading the human immune system by directly interacting with a receptor called TANK-binding kinase (TBK1), leading to the suppression of IFNp production. Consequently, in the present study we used the structural and biophysical approaches to analyze the effect of newly emerged mutations on the binding of NSP6 and TBK1. Among the identified mutations, four (F35G, L37F, L125F, and I162T) were found to significantly destabilize the structure of NSP6. Furthermore, the molecular docking analysis highlighted that the mutant NSP6 displayed its highest binding affinity with TBK1, exhibiting docking scores of-1436.2 for the wildtype and-1723.2,-1788.6,-1510.2, and-1551.7 for the F35G, L37F, L125F, and I162T mutants, respectively. This suggests the potential for an enhanced immune system evasion capability of NSP6. Particularly, the F35G mutation exhibited the strongest binding affinity, supported by a calculated binding free energy of-172.19 kcal/mol. To disrupt the binding between NSP6 and TBK1, we conducted virtual drug screening to develop a novel inhibitor derived from natural products. From this screening, we identified the top 5 hit compounds as the most promising candidates with a docking score of-6.59 kcal/mol,-6.52 kcal/mol,-6.32 kcal/mol,-6.22 kcal/mol, and-6.21 kcal/mol. The molecular dynamic simulation of top 3 hits further verified the dynamic stability of drugs-NSP6 complexes. In conclusion, this study provides valuable insight into the higher infectivity of the SARS-CoV-2 new variants and a strong rationale for the development of novel drugs against NSP6. [ABSTRACT FROM AUTHOR]

Foot-and-mouth disease (FMD) is a highly infectious animal disease caused by foot-and-mouth disease virus (FMDV) and primarily infects cloven-hoofed animals such as cattle, sheep, goats, and pigs. It has become a significant health concern in global livestock industries because of diverse serotypes, high mutation rates, and contagious nature. There is no specific antiviral treatment available for FMD. Hence, based on the importance of 3C protease in FMDV viral replication and pathogenesis, we have employed a structure-based virtual screening method by targeting 3C protease with a natural compounds dataset (n = 69,040) from the InterBioScreen database. Virtual screening results identified five potential compounds, STOCK1N-62634, STOCK1N-96109, STOCK1N-94672, STOCK1N-89819, and STOCK1N-80570, with a binding affinity of -9.576 kcal/mol, -8.1 kcal/mol, -7.744 kcal/mol, -7.647 kcal/mol, and - 7.778 kcal/mol, respectively. The compounds were further validated through physiochemical properties and density functional theory (DFT). Subsequently, the comparative 300-ns MD simulation of all five complexes exhibited overall structural stability from various MD analyses such as root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), solvent accessible surface area (SASA), H-bonds, principal component analysis (PCA), and free energy landscape (FEL). Furthermore, MM-PBSA calculation suggests that all five compounds, particularly STOCK1N-62634, STOCK1N-96109, and STOCK1N-94672, can be considered as potential inhibitors because of their strong binding affinity toward 3C protease. Thus, we hope that these identified compounds can be studied extensively to develop natural therapeutics for the better management of FMD. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surfaced on 31 December, 2019, and was identified as the causative agent of the global COVID-19 pandemic, leading to a pneumonia-like disease. One of its accessory proteins, ORF6, has been found to play a critical role in immune evasion by interacting with KPNA2 to antagonize IFN signaling and production pathways, resulting in the inhibition of IRF3 and STAT1 nuclear translocation. Since various mutations have been observed in ORF6, therefore, a comparative binding, biophysical, and structural analysis was used to reveal how these mutations affect the virus's ability to evade the human immune system. Among the identifiedmutations, the V9F, V24A,W27L, and I33T, were found to have a highly destabilizing effect on the protein structure of ORF6. Additionally, the molecular docking analysis of wildtype andmutant ORF6 and KPNA2 revealed the docking score of - 53.72 kcal/mol for wildtype while, -267.90 kcal/mol, -258.41kcal/mol, -254.51 kcal/mol and -268.79 kcal/mol for V9F, V24A, W27L, and I33T respectively. As compared to the wildtype the V9F showed a stronger binding affinity with KPNA2 which is further verified by the binding free energy (-42.28 kcal/mol) calculation. Furthermore, to halt the binding interface of the ORF6-KPNA2 complex, we used a computational molecular search of potential natural products. A multi-step virtual screening of the African natural database identified the top 5 compounds with best docking scores of -6.40 kcal/mol, -6.10 kcal/mol, -6.09 kcal/mol, -6.06 kcal/mol, and -6.03 kcal/mol for tophit1-5 respectively. Subsequent all-atoms simulations of these top hits revealed consistent dynamics, indicating their stability and their potential to interact effectively with the interface residues. In conclusion, our study represents the first attempt to establish a foundation for understanding the heightened infectivity of new SARS-CoV-2 variants and provides a strong impetus for the development of novel drugs against them. [ABSTRACT FROM AUTHOR]

Amid the ongoing monkeypox outbreak, there is an urgent need for the rapid development of effective therapeutic interventions capable of countering the immune evasion mechanisms employed by the monkeypox virus (MPXV). The evasion strategy involves the binding of the F3L protein to dsRNA, resulting in diminished interferon (IFN) production. Consequently, our current research focuses on utilizing virtual drug screening techniques to target the RNA binding domain of the F3L protein. Out of the 954 compounds within the South African natural compound database, only four demonstrated notable docking scores: −6.55, −6.47, −6.37, and −6.35 kcal/mol. The dissociation constant (KD) analysis revealed a stronger binding affinity of the top hits 1-4 (−5.34, −5.32, −5.29, and −5.36 kcal/mol) with the F3L in the MPXV. All-atom simulations of the top-ranked hits 1 to 4 consistently exhibited stable dynamics, suggesting their potential to interact effectively with interface residues. This was further substantiated through analyses of parameters such as radius of gyration (Rg), Root Mean Square Fluctuation, and hydrogen bonding. Cumulative assessments of binding free energy confirmed the top-performing candidates among all the compounds, with values of −35.90, −52.74, −28.17, and −32.11 kcal/ mol for top hits 1-4, respectively. These results indicate that compounds top hit 1- 4 could hold significant promise for advancing innovative drug therapies, suggesting their suitability for both in vivo and in vitro experiments. [ABSTRACT FROM AUTHOR]

The present investigation utilized in silico methodologies to explore the diverse pharmacological activities, toxicity profiles, and chemical reactivity of a series of fluoro‐flavonoid compounds (1–14), which are secondary metabolites of plants known for their broad range of biological effects. A comprehensive strategy is utilized, incorporating methods such as prediction of activity spectra for substances (PASS) prediction, absorption, distribution, metabolism, excretion, and toxicity (ADMET) assessments, and density functional theory (B3LYP) calculations using three basis sets: 6‐31G(d,p), 6‐311G(d,p), and 6‐311++G(d,p). Furthermore, the study employed molecular docking technique to identify target proteins, including HER2 (7JXH), EGFR (4UV7), FPPS (1YQ7), HPGDS (1V40), DCK (1P60), and KEAP1 on Nrf2 (1X2J), for the investigated compounds, with cianidanol and genistein serving as reference drugs for the docking process. The investigated fluoro‐flavonoid compounds exhibited significantly greater binding affinities (ranging from −8.3 to −10.6 kcal mol−1) toward HER2, HPGDS, and KEAP1 compared to the reference drugs, cianidanol and genistein, which displayed binding affinities ranging from −8.4 to −9.4 kcal mol−1. Furthermore, molecular dynamics simulations were conducted to assess the stability of the protein‐ligand interaction, using the root‐mean‐square deviation (RMSD), root‐mean‐square fluctuation (RMSF), Radius of gyration (Rg) parameters and principle component analysis (PCA). Among the tested fluoro‐flavonoid analogs, analog 11 showed a RMSD value of.15 nm with the HER2 protein target, indicating a stable interaction. Based on in silico results, it appears that the fluoro‐flavonoid compound 11 has the potential to serve as a targeted anti‐lung cancer drug. However, additional in vivo and in vitro studies are necessary to confirm this hypothesis. [ABSTRACT FROM AUTHOR]