cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.28532894.v1
title: Network pharmacology exploring the mechanistic role of indirubin phytoconstituent from <i>Indigo naturalis</i> targeting GSK-3<i>β</i> in Alzheimer’s disease

description: One of the most common causes of dementia in older adults is Alzheimer’s disease (AD). Numerous mechanisms, including acetylcholine breakdown, amyloid beta buildup, neurofibrillary tangle accumulation, and inflammation, are involved in the pathogenesis of AD. Different targets have been demonstrated in studies to alleviate the cognitive impairment in AD. In AD, amyloid <i>β</i> impairs phosphatidylinositol-3 (PI3)/Akt signaling, activating GSK-3<i>β</i>. This sequence leads to an increase in the phosphorylation of tau, the creation of neurofibrillary tangles, neuronal death, loss of synapses, and memory impairments, all of which are typical symptoms seen in the brains of individuals with AD. Using network pharmacology, molecular docking, and MD simulations, we have determined that indirubin can selectively interact with glycogen synthase kinase 3 beta (GSK-3<i>β</i>). Traditional Chinese Medicine, including <i>Indigo naturalis, is</i> known to have the ability to control chronic diseases having indirubin as the main phytoconstituent. The binding energy of indirubin was −10.9 kcal/mol, which was better than that of the reference ligand with −9.4 kcal/mol. According to MD simulations, the indirubin-GSK-3<i>β</i> complex remained stable during the simulation, exhibiting an RMSD of 1.90 in comparison to the 2.01 and 2.34 for reference-GSK-3<i>β</i> complex and free protein, respectively. According to our study, indirubin phytoconstituent from <i>Indigo naturalis</i>, targets GSK-3β in AD, additional investigation in the quest for inhibitors of this crucial biological target required further in-vitro/in-vivo experimental validations.
DOI: 10.6084/m9.figshare.28740941
title: Understanding of ATP-lid conformational dynamics in the N-terminal domain of Hsp90 and its mutants by use of a computational biochemistry approach

description: Chaperone Hsp90 regulates the activation and maturation of various protein, and is an attractive target for drug discovery. In catalytic cycle of Hsp90, ATP hydrolysis is a key event that drives structural changes, including the interchange of the dimeric Hsp90 structure between open and closed forms. For ATP hydrolysis, ATP-lid closure in the ATP-binding site from the up- to down-conformation is an indispensable co-ordinated structural change. However, the atomistic mechanism underlying lid closure remains unclear. In this study, a computational biochemistry approach was applied to wild-type apo and ATP-complex structures, and the lid-mutants A107N and T101I ATP-complex, to understand lid closure. A total of 15-μs molecular dynamic simulation, including the equilibration and production phases, was conducted for every structure starting from the lid up-conformation, but no lid-closures were observed. However, a very early event, i.e. <i>a sign</i>, of lid closure have been captured. In the simulations of wild-type and A107N ATP-complex structures, lid segment showed conformational fluctuations, and helix-7 (H7) segment in lid segment was unwound. This conformational instability of lid segment energetically weakened its interaction with facing region, suggesting the up-to-down transition was triggered by the instability of lid segment, particularly H7 segment. The interaction energy between lid segment and facing region was ranked in the order A107N &gt; wild-type &gt; T101I, which was correlated with experimental results such as the orders of ATP-hydrolytic activity and rapidity of conformational changes of lid segment, measured in ATP-spiking experiments by fluorescence resonance energy transfer method (i.e. A107N &gt; wild-type &gt; T101I).
DOI: 10.6084/m9.figshare.28740941.v1
title: Understanding of ATP-lid conformational dynamics in the N-terminal domain of Hsp90 and its mutants by use of a computational biochemistry approach

description: Chaperone Hsp90 regulates the activation and maturation of various protein, and is an attractive target for drug discovery. In catalytic cycle of Hsp90, ATP hydrolysis is a key event that drives structural changes, including the interchange of the dimeric Hsp90 structure between open and closed forms. For ATP hydrolysis, ATP-lid closure in the ATP-binding site from the up- to down-conformation is an indispensable co-ordinated structural change. However, the atomistic mechanism underlying lid closure remains unclear. In this study, a computational biochemistry approach was applied to wild-type apo and ATP-complex structures, and the lid-mutants A107N and T101I ATP-complex, to understand lid closure. A total of 15-μs molecular dynamic simulation, including the equilibration and production phases, was conducted for every structure starting from the lid up-conformation, but no lid-closures were observed. However, a very early event, i.e. <i>a sign</i>, of lid closure have been captured. In the simulations of wild-type and A107N ATP-complex structures, lid segment showed conformational fluctuations, and helix-7 (H7) segment in lid segment was unwound. This conformational instability of lid segment energetically weakened its interaction with facing region, suggesting the up-to-down transition was triggered by the instability of lid segment, particularly H7 segment. The interaction energy between lid segment and facing region was ranked in the order A107N &gt; wild-type &gt; T101I, which was correlated with experimental results such as the orders of ATP-hydrolytic activity and rapidity of conformational changes of lid segment, measured in ATP-spiking experiments by fluorescence resonance energy transfer method (i.e. A107N &gt; wild-type &gt; T101I).
DOI: 10.6084/m9.figshare.28682835
title: Direct current electric field exposure changes the conformational dynamics of IL-1β in RAW 264.7 macrophages

description: Wearable devices have led to a growing interest in the effects of physical stimuli, such as electric fields (EF), on cells. However, the impact of EF on macrophages remains largely unexplored. To address this gap, we developed an electric-field chamber that applies direct current electric field (dcEF) to RAW 264.7 macrophages and analyzed the transcriptome changes and IL-1β protein conformation dynamics. Our results showed that exposure to dcEF did not affect cell morphology but significantly reduced cell viability. RNA-seq analysis revealed that dcEF altered the expression of 3518 upregulated and 2,531 downregulated genes. We also identified 6 hub genes using PPI network analysis and qPCR test. In addition, WB results suggested that dcEF increased the expression level of IL-1β. Next, we used molecular dynamics (MD) simulations to investigate the impact of dcEF on the conformation of the IL-1β protein. Our analysis results indicate that the dcEF’s intensity significantly impacts various aspects of protein behavior, including its structure, motion, hydrogen bonding, and dipole moment. The alpha-helix structure exhibited the earliest degradation when exposed to an electric field, destroying other natural structures. In addition, the results of interleukin-1 (IL-1) gene family analysis suggest that this gene family is evolutionarily highly conserved. Overall, our findings provide insights into the influence of dcEF on macrophages and suggest potential applications of dcEF in cell biology and medicine.
DOI: 10.6084/m9.figshare.28682835.v1
title: Direct current electric field exposure changes the conformational dynamics of IL-1β in RAW 264.7 macrophages

description: Wearable devices have led to a growing interest in the effects of physical stimuli, such as electric fields (EF), on cells. However, the impact of EF on macrophages remains largely unexplored. To address this gap, we developed an electric-field chamber that applies direct current electric field (dcEF) to RAW 264.7 macrophages and analyzed the transcriptome changes and IL-1β protein conformation dynamics. Our results showed that exposure to dcEF did not affect cell morphology but significantly reduced cell viability. RNA-seq analysis revealed that dcEF altered the expression of 3518 upregulated and 2,531 downregulated genes. We also identified 6 hub genes using PPI network analysis and qPCR test. In addition, WB results suggested that dcEF increased the expression level of IL-1β. Next, we used molecular dynamics (MD) simulations to investigate the impact of dcEF on the conformation of the IL-1β protein. Our analysis results indicate that the dcEF’s intensity significantly impacts various aspects of protein behavior, including its structure, motion, hydrogen bonding, and dipole moment. The alpha-helix structure exhibited the earliest degradation when exposed to an electric field, destroying other natural structures. In addition, the results of interleukin-1 (IL-1) gene family analysis suggest that this gene family is evolutionarily highly conserved. Overall, our findings provide insights into the influence of dcEF on macrophages and suggest potential applications of dcEF in cell biology and medicine.
DOI: 10.6084/m9.figshare.27861115
title: Paclitaxel and myricetin encapsulated hemoglobin nanoparticles: characterization and application

description: Hb is used as a carrier protein to encapsulate hydrophobic drugs PTX and MYN and has applications in cancer treatment. PTX and MYN encapsulated Hb NPs are synthesized by the acid denature method and are characterized by spectroscopic and electron microscopic techniques. The binding constant calculated for Hb and PTX is 3.83 x 10<sup>8</sup> M<sup>-1</sup>, which is the highest in the pH range tested for both drugs. The CD spectra also demonstrated maximum denaturation of Hb at pH 5.0 evidencing the opening of the Hb hydrophobic core. The acidic condition at pH 5.0 is optimized for the synthesis of drug- encapsulated NPs. FTIR spectra of Hb PTX NPs recorded higher shifts in the OH/carboxyl peak compared to Hb-MYN. SEM images of Hb-PTX NPs highlight the tetrahedral structure of the NPs and the round shape of Hb-MYN NPs. The size of Hb-MYN and Hb-PTX is around 38.0 and 44.0 nm respectively as measured by DLS. PTX-Hb NPs demonstrated higher dose-dependent apoptosis-inducing efficacy than MYN-Hb in the K562 cells.
DOI: 10.6084/m9.figshare.27861115.v1
title: Paclitaxel and myricetin encapsulated hemoglobin nanoparticles: characterization and application

description: Hb is used as a carrier protein to encapsulate hydrophobic drugs PTX and MYN and has applications in cancer treatment. PTX and MYN encapsulated Hb NPs are synthesized by the acid denature method and are characterized by spectroscopic and electron microscopic techniques. The binding constant calculated for Hb and PTX is 3.83 x 10<sup>8</sup> M<sup>-1</sup>, which is the highest in the pH range tested for both drugs. The CD spectra also demonstrated maximum denaturation of Hb at pH 5.0 evidencing the opening of the Hb hydrophobic core. The acidic condition at pH 5.0 is optimized for the synthesis of drug- encapsulated NPs. FTIR spectra of Hb PTX NPs recorded higher shifts in the OH/carboxyl peak compared to Hb-MYN. SEM images of Hb-PTX NPs highlight the tetrahedral structure of the NPs and the round shape of Hb-MYN NPs. The size of Hb-MYN and Hb-PTX is around 38.0 and 44.0 nm respectively as measured by DLS. PTX-Hb NPs demonstrated higher dose-dependent apoptosis-inducing efficacy than MYN-Hb in the K562 cells.
DOI: 10.6084/m9.figshare.29137600
title: Network pharmacology and molecular docking approach to predict the oral and topical therapeutic mechanisms of <i>Panax ginseng</i>’s active compounds on atopic dermatitis

description: Atopic dermatitis (AD) is a recurrent inflammatory skin condition marked by itching, inflammation, and lichenification, primarily affecting children. <i>Panax ginseng</i> shows therapeutic promise in treating AD, although research on its mechanisms remains limited. For the first time, a network pharmacology approach was used to explore the pharmacological mechanisms of <i>Panax ginseng</i>’s active compounds in AD treatment. Screening for bioactive compounds and their respective targets was conducted through the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and SwissTargetPrediction databases. AD-related targets were gathered from GeneCards, DisGeNET, and OMIM databases. The VENNY tool was used to identify overlapping targets. STRING 12.0 was utilized for protein-protein interaction (PPI) network analysis, Cytoscape for network construction, DAVID for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and PyRx AutoDock Vina for molecular docking. We retrieved 14 bioactive compounds (oral bioavailability ≥ 30% and drug-likeness ≥ 0.18) from <i>Panax ginseng</i>, corresponding to 552 targets, and 44 compounds (OB &lt; 30% and DL ≥ 0.18) with 610 potential targets for oral and topical AD therapies. In the compound-target network, Gomisin B, Kaempferol, Celabenzine, and Panaxadiol emerged as key oral compounds targeting hub genes. Ginsenoside-Rh3, 12-O-nicotinoylisolineolone, Ginsenoside-Rh4, and Panaxatriol were linked to hub genes, suggesting topical application potential. GO and KEGG enrichment showed involvement of Th17 cell differentiation, EGFR tyrosine kinase inhibitor resistance, C-type lectin receptor signaling, and TNF signaling. Molecular docking showed strong binding between key compounds and core targets. This study highlights <i>Panax ginseng</i>’s potential in complementary AD treatment.
DOI: 10.6084/m9.figshare.29137600.v1
title: Network pharmacology and molecular docking approach to predict the oral and topical therapeutic mechanisms of <i>Panax ginseng</i>’s active compounds on atopic dermatitis

description: Atopic dermatitis (AD) is a recurrent inflammatory skin condition marked by itching, inflammation, and lichenification, primarily affecting children. <i>Panax ginseng</i> shows therapeutic promise in treating AD, although research on its mechanisms remains limited. For the first time, a network pharmacology approach was used to explore the pharmacological mechanisms of <i>Panax ginseng</i>’s active compounds in AD treatment. Screening for bioactive compounds and their respective targets was conducted through the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and SwissTargetPrediction databases. AD-related targets were gathered from GeneCards, DisGeNET, and OMIM databases. The VENNY tool was used to identify overlapping targets. STRING 12.0 was utilized for protein-protein interaction (PPI) network analysis, Cytoscape for network construction, DAVID for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and PyRx AutoDock Vina for molecular docking. We retrieved 14 bioactive compounds (oral bioavailability ≥ 30% and drug-likeness ≥ 0.18) from <i>Panax ginseng</i>, corresponding to 552 targets, and 44 compounds (OB &lt; 30% and DL ≥ 0.18) with 610 potential targets for oral and topical AD therapies. In the compound-target network, Gomisin B, Kaempferol, Celabenzine, and Panaxadiol emerged as key oral compounds targeting hub genes. Ginsenoside-Rh3, 12-O-nicotinoylisolineolone, Ginsenoside-Rh4, and Panaxatriol were linked to hub genes, suggesting topical application potential. GO and KEGG enrichment showed involvement of Th17 cell differentiation, EGFR tyrosine kinase inhibitor resistance, C-type lectin receptor signaling, and TNF signaling. Molecular docking showed strong binding between key compounds and core targets. This study highlights <i>Panax ginseng</i>’s potential in complementary AD treatment.
DOI: 10.6084/m9.figshare.28574719
title: Structural basis of multi-target interactions of Henna Dye Lawsone: an experimental and theoretical evaluation

description: Lawsone (2-hydroxy-1,4-naphthoquinone), also known as hennotannic acid, is a red-orange dye present in the leaves of the henna plant (<i>Lawsonia inermis</i>) having lots of biological activities. In this paper, we have investigated the structural basis of binding affinities of Lawsone towards two different targets namely, calf thymus DNA (CT-DNA) and protein bovine serum albumin (BSA) using experimental and computational approaches. This phytochemical binds to the minor groove of DNA and Sudlow site II, Domain III of BSA. The binding constants obtained from spectroscopic studies for Lawsone with DNA and BSA have been determined as 1.79 × 10³ M<sup>−1</sup> and 2.18 × 10³ M<sup>−1</sup>, respectively with corresponding Gibbs free energies of −4.46 kcal/mol and −4.58 kcal/mol. Conformational changes in the secondary structures of the receptors upon binding with Lawsone is observed. Isothermal titration calorimetry (ITC) experiments reveal that binding is favoured mainly due to negative enthalpy changes (−18.2 kcal/mol for DNA and −98.77 kcal/mol for BSA). Molecular docking and dynamics simulations elucidate intermolecular contacts between Lawsone and the receptors, providing insight into the energetic profile of the complexes and revealing Lawsone’s reorientation within the binding sites. Both experimental and computational findings highlight the significance of hydrogen bonding and hydrophobic interactions in the binding process, offering valuable insights into Lawsone’s molecular interactions with biomolecules and its potential therapeutic applications.
DOI: 10.6084/m9.figshare.28574719.v1
title: Structural basis of multi-target interactions of Henna Dye Lawsone: an experimental and theoretical evaluation

description: Lawsone (2-hydroxy-1,4-naphthoquinone), also known as hennotannic acid, is a red-orange dye present in the leaves of the henna plant (<i>Lawsonia inermis</i>) having lots of biological activities. In this paper, we have investigated the structural basis of binding affinities of Lawsone towards two different targets namely, calf thymus DNA (CT-DNA) and protein bovine serum albumin (BSA) using experimental and computational approaches. This phytochemical binds to the minor groove of DNA and Sudlow site II, Domain III of BSA. The binding constants obtained from spectroscopic studies for Lawsone with DNA and BSA have been determined as 1.79 × 10³ M<sup>−1</sup> and 2.18 × 10³ M<sup>−1</sup>, respectively with corresponding Gibbs free energies of −4.46 kcal/mol and −4.58 kcal/mol. Conformational changes in the secondary structures of the receptors upon binding with Lawsone is observed. Isothermal titration calorimetry (ITC) experiments reveal that binding is favoured mainly due to negative enthalpy changes (−18.2 kcal/mol for DNA and −98.77 kcal/mol for BSA). Molecular docking and dynamics simulations elucidate intermolecular contacts between Lawsone and the receptors, providing insight into the energetic profile of the complexes and revealing Lawsone’s reorientation within the binding sites. Both experimental and computational findings highlight the significance of hydrogen bonding and hydrophobic interactions in the binding process, offering valuable insights into Lawsone’s molecular interactions with biomolecules and its potential therapeutic applications.
DOI: 10.15468/dl.729ev4
title: Occurrence Download

description: A dataset containing 1 species occurrences available in GBIF matching the query:
{
 "and" : [
 "TaxonKey is Ulmus pumila",
 "HasCoordinate is true",
 "BasisOfRecord is one of (Specimen)"
 ]
}

 The dataset includes 1 records from 1 constituent datasets; see https://api.gbif.org/v1/occurrence/download/0000089-260129131611470/datasets/export for details.
 
Data from some individual datasets included in this download may be licensed under less restrictive terms.
DOI: 10.6084/m9.figshare.29313601
title: Synthesis, structure, DNA docking, pharmacokinetics/ADMET, Hirshfeld surface analysis, and antimicrobial studies on biphenyl appended pyrrolidine complexes

description: Biphenyl anchored pyrrolidine complexes [MLCl<sub>2</sub>], [where M = Co (<b>1</b>), Ni (<b>2</b>), Cu (<b>3</b>) and Zn (<b>4</b>); <b><i>L</i> </b>=<b> </b>6-(2-(pyrrolidin-1-yl)ethyl)-6,7-dihydro-5H-dibenzo[c,e]azepine] were synthesized and characterized by elemental analysis, UV-Vis, FT-IR, ESI-MS, and NMR (in case of <b>4</b>). Single crystal XRD revealed that all the complexes adopt distorted tetrahedral geometry. DFT calculations with their relative energies were compared with XRD structure. Absorption, oscillator strength, excitation energy, molecular orbital contributions were obtained from TDDFT calculation. The computed UV-Vis absorption data is comparable with experimental UV-Vis data. Molecular docking studies verified that all complexes strongly bind with DNA (PDB ID: 1BNA) through major groove interactions. The ligand and the complexes exhibit an elevated permeability of the blood-brain barrier and GI absorption, according to the SwissADME prediction criteria. The values of skin permeability (logKp) for the ligand and complexes <b>1-4</b> were determined to be −5.61, −5.27, −5.27, −5.30, and −5.31 cms<sup>−1</sup>, respectively. All the complexes and the ligand were projected to function as a biological barrier, a transporter, and a substrate of P-glycoprotein (P-gp), which is responsible for the ADME of medications. Using Hirshfeld surface investigation, the intermolecular interactions within the crystal network were identified to support the prominent contribution from H∙∙∙∙∙H interactions, followed by Cl∙∙∙∙∙H and C∙∙∙∙∙H interactions, respectively. In the preliminary investigations, all the complexes displayed significant antibacterial properties against both Gram-positive and Gram-negative bacterial strains such as Staphylococcus aureus and Escherichia coli, respectively; those were obtained from human clinical isolates. Notably, the copper(II) complex, <b>3</b> showed better antibacterial activity in comparison to other complexes. Biphenyl appended pyrrolidine complexes [MLCl<sub>2</sub>] were symthesized.The geometry and interaction energy were assessed via DFT and Hirschfeld surface analysis.Docking analyses verified the binding of all complexes with DNA.To predict pharmacokinetic properties, an in silico ADMET study was conducted.Copper complex showed better antibacterial activity. Biphenyl appended pyrrolidine complexes [MLCl<sub>2</sub>] were symthesized. The geometry and interaction energy were assessed via DFT and Hirschfeld surface analysis. Docking analyses verified the binding of all complexes with DNA. To predict pharmacokinetic properties, an in silico ADMET study was conducted. Copper complex showed better antibacterial activity.