cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.24218630.v1
title: Integrating network pharmacology with molecular docking for elucidation of molecular biological mechanisms of Jiedu Qingjin formula for non-small cell lung cancer

description: Traditional Chinese medicine is an important part of complementary alternative medicine. Jiedu Qingjin formula (JDQJF) is an effective national invention patent for the treatment of non-small cell lung cancer (NSCLC). We investigated the molecular biological mechanisms based on network pharmacology, molecular docking, and molecular dynamics simulations. Compounds of JDQJF were screened through the TCMSP, ETCM, and literature. Targets were searched by DrugBank and predicted by SwissTargetPrediction. GEO database was applied for screening differentially expressed genes between cancerous tissues and healthy tissues of NSCLC. Subsequently, the protein-protein interaction between JDQJF and NSCLC were obtained by Cytoscape. Visual analyses were carried out to extract candidate genes, then subjected to Metascape for enrichment analyses. Finally, molecular docking was performed by AutoDock, and the best complexes were subjected to molecular dynamics simulation and binding energy calculations by MMPBSA. A total of 273 compounds, 390 targets, 3146 GO terms, and 174 KEGG pathways were obtained. Five potential compounds (quercetin, adenosine, apigenin, heptadecanoic acid, and luteolin) were notably modulated by key targets <i>AKT1, MAPK3,</i> and <i>RAF1</i>. Enrichment results included cell cycle process, growth transduction factor, immune response-activating transduction, and involved PI3K/AKT, MAPK, NF-κB and VEGF pathway. <i>RAF1</i>-quercetin showed the highest binding affinity (-9.1 kcal/mol), revealed stable interactions during the simulation, and the highest estimated relative binding energy of the <i>RAF1</i>-Heptadecanoic was −184.277 kcal/mol. This study suggested that EMT-related, inflammation-related, immune-related, and angiogenesis-related pathways may be associated with JDQJF, and involved in the advancement of NSCLC, which points out the research direction for subsequent utility mechanism validation. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.24212149.v1
title: Computational investigation on the effect of the peptidomimetic inhibitors (NPT100-18A and NPT200-11) on the α-synuclein and lipid membrane interactions

description: Parkinson’s disease (PD) is associated with α-synuclein (α-Syn), a presynaptic protein that binds to cell membranes. The molecular pathophysiology of PD most likely begins with the binding of α-Syn to membranes. Recently, two peptidomimetic inhibitors (NPT100-18A and NPT200-11) were identified to potentially interact with α-Syn and affect the interaction of α-Syn with the membrane. In this study, the effect of the two peptidomimetic inhibitors on the α-Syn-membrane interaction was demonstrated. DFT calculations were performed for optimization of the two inhibitors, and the nucleophilicity (N) and electrophilicity (ω) of NPT100-18A and NPT200-11 were calculated to be 3.90 and 3.86 (N); 1.06 and 1.04 (ω), respectively. Using the docking tool (CB-dock2), the two α-Syn-peptidomimetic inhibitor complexes (α-Syn-NPT100-18A and α-Syn-NPT200-11) have been prepared. Then all-atom molecular dynamics (MD) simulation was carried out on the α-Syn (control), α-Syn-NPT100-18A and α-Syn-NPT200-11 complex systems in presence of DOPE: DOPS: DOPC (5:3:2) lipid bilayer. From the conformational dynamics analysis, the 3-D structure of α-Syn was found to be stable, and the helices present in the regions (1–37) and (45–95) of α-Syn were found to be retained in the presence of the two peptidomimetic inhibitors. The electron density profile analysis revealed the binding modes of NAC and C-terminal region of α-Syn (in the presence of NPT200-11 inhibitor) with lipid membrane are in the close vicinity from the lipid bilayer centre. Our findings in this study on α-Syn-membrane interactions may be useful for developing a new therapeutic approach for treating PD and other neurodegenerative disorders. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.24212149
title: Computational investigation on the effect of the peptidomimetic inhibitors (NPT100-18A and NPT200-11) on the α-synuclein and lipid membrane interactions

description: Parkinson’s disease (PD) is associated with α-synuclein (α-Syn), a presynaptic protein that binds to cell membranes. The molecular pathophysiology of PD most likely begins with the binding of α-Syn to membranes. Recently, two peptidomimetic inhibitors (NPT100-18A and NPT200-11) were identified to potentially interact with α-Syn and affect the interaction of α-Syn with the membrane. In this study, the effect of the two peptidomimetic inhibitors on the α-Syn-membrane interaction was demonstrated. DFT calculations were performed for optimization of the two inhibitors, and the nucleophilicity (N) and electrophilicity (ω) of NPT100-18A and NPT200-11 were calculated to be 3.90 and 3.86 (N); 1.06 and 1.04 (ω), respectively. Using the docking tool (CB-dock2), the two α-Syn-peptidomimetic inhibitor complexes (α-Syn-NPT100-18A and α-Syn-NPT200-11) have been prepared. Then all-atom molecular dynamics (MD) simulation was carried out on the α-Syn (control), α-Syn-NPT100-18A and α-Syn-NPT200-11 complex systems in presence of DOPE: DOPS: DOPC (5:3:2) lipid bilayer. From the conformational dynamics analysis, the 3-D structure of α-Syn was found to be stable, and the helices present in the regions (1–37) and (45–95) of α-Syn were found to be retained in the presence of the two peptidomimetic inhibitors. The electron density profile analysis revealed the binding modes of NAC and C-terminal region of α-Syn (in the presence of NPT200-11 inhibitor) with lipid membrane are in the close vicinity from the lipid bilayer centre. Our findings in this study on α-Syn-membrane interactions may be useful for developing a new therapeutic approach for treating PD and other neurodegenerative disorders. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.24218626
title: Design of a novel multi-epitope vaccine candidate against endometrial cancer using immunoinformatics and bioinformatics approaches

description: Endometrial cancer (EC) is one of the most common cancers of the female reproductive system. Multi-epitope vaccine may be a promising and effective strategy against EC. In this study, we designed a novel multi-epitope vaccine based on the antigenic proteins PRAME and TMPRSS4 using immunoinformatics and bioinformatics approaches. After a rigorous selection process, 14 cytotoxic T lymphocyte (CTL) epitopes, 6 helper T lymphocyte (HTL) epitopes, and 8 B cell epitopes (BCEs) were finally selected for vaccine construction. To enhance the immunogenicity of the vaccine candidate, the pan HLA DR-binding epitope was included in the vaccine design as an adjuvant. The final vaccine construct had 455 amino acids and a molecular weight of 49.8 kDa, and was predicted to cover 95.03% of the total world population. Docking analysis showed that there were 10 hydrogen bonds and 19 hydrogen bonds in the vaccine-HLA-A*02:01 and vaccine-HLA-DRB1*01:01 complexes, respectively, indicating that the vaccine has a good affinity to MHC molecules. This was further supported by molecular dynamics (MD) simulation. Immune simulation showed that the designed vaccine was able to induce higher levels of immune cell activity, with the secretion of numerous cytokines. The codon adaptation index (CAI) value and GC content of the optimised codon sequences of the vaccine were 0.986 and 54.43%, respectively, indicating that the vaccine has the potential to be highly expressed. The in silico analysis suggested that the designed vaccine may provide a novel therapeutic option for the individualised treatment of EC patients in the future. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.24218626.v1
title: Design of a novel multi-epitope vaccine candidate against endometrial cancer using immunoinformatics and bioinformatics approaches

description: Endometrial cancer (EC) is one of the most common cancers of the female reproductive system. Multi-epitope vaccine may be a promising and effective strategy against EC. In this study, we designed a novel multi-epitope vaccine based on the antigenic proteins PRAME and TMPRSS4 using immunoinformatics and bioinformatics approaches. After a rigorous selection process, 14 cytotoxic T lymphocyte (CTL) epitopes, 6 helper T lymphocyte (HTL) epitopes, and 8 B cell epitopes (BCEs) were finally selected for vaccine construction. To enhance the immunogenicity of the vaccine candidate, the pan HLA DR-binding epitope was included in the vaccine design as an adjuvant. The final vaccine construct had 455 amino acids and a molecular weight of 49.8 kDa, and was predicted to cover 95.03% of the total world population. Docking analysis showed that there were 10 hydrogen bonds and 19 hydrogen bonds in the vaccine-HLA-A*02:01 and vaccine-HLA-DRB1*01:01 complexes, respectively, indicating that the vaccine has a good affinity to MHC molecules. This was further supported by molecular dynamics (MD) simulation. Immune simulation showed that the designed vaccine was able to induce higher levels of immune cell activity, with the secretion of numerous cytokines. The codon adaptation index (CAI) value and GC content of the optimised codon sequences of the vaccine were 0.986 and 54.43%, respectively, indicating that the vaccine has the potential to be highly expressed. The in silico analysis suggested that the designed vaccine may provide a novel therapeutic option for the individualised treatment of EC patients in the future. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.24271258
title: Immunoinformatics aided designing of a next generation poly-epitope vaccine against uropathogenic <i>Escherichia coli</i> to combat urinary tract infections

description: Urinary tract infections (UTIs) are the second most prevalent bacterial infections and uropathogenic <i>Escherichia coli</i> (UPEC) stands among the primary causative agents of UTIs. The usage of antibiotics is the routine therapy being used in various countries to treat UTIs but becoming ineffective because of increasing antibiotic resistance among UPEC strains. Thus, there must be the development of some alternative treatment strategies such as vaccine development against UPEC. In the following study, pan-genomics along with reverse vaccinology approaches is used under the framework of bioinformatics for the identification of core putative vaccine candidates, employing 307 UPEC genomes (complete and draft), available publicly. A total of nine T-cell epitopes (derived from B-cells) of both MHC classes (I and II), were prioritized among three potential protein candidates. These epitopes were then docked together by using linkers (GPGPG and AAY) and an adjuvant (Cholera Toxin B) to form a poly-valent vaccine construct. The chimeric vaccine construct was undergone by molecular modelling, further refinement and energy minimization. We predicted positive results of the vaccine construct in immune simulations with significantly high levels of immune cells. The protein-protein docking analysis of vaccine construct with toll-like receptors predicted efficient binding, which was further validated by molecular dynamics simulation of vaccine construct with TLR-2 and TLR-4 at 120 ns, resulting in stable complexes’ conformation throughout the simulation run. Overall, the vaccine construct demonstrated positive antigenic response. In future, this chimeric vaccine construct or the identified epitopes could be experimentally validated for the development of UPEC vaccines against UTIs. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.24271258.v1
title: Immunoinformatics aided designing of a next generation poly-epitope vaccine against uropathogenic <i>Escherichia coli</i> to combat urinary tract infections

description: Urinary tract infections (UTIs) are the second most prevalent bacterial infections and uropathogenic <i>Escherichia coli</i> (UPEC) stands among the primary causative agents of UTIs. The usage of antibiotics is the routine therapy being used in various countries to treat UTIs but becoming ineffective because of increasing antibiotic resistance among UPEC strains. Thus, there must be the development of some alternative treatment strategies such as vaccine development against UPEC. In the following study, pan-genomics along with reverse vaccinology approaches is used under the framework of bioinformatics for the identification of core putative vaccine candidates, employing 307 UPEC genomes (complete and draft), available publicly. A total of nine T-cell epitopes (derived from B-cells) of both MHC classes (I and II), were prioritized among three potential protein candidates. These epitopes were then docked together by using linkers (GPGPG and AAY) and an adjuvant (Cholera Toxin B) to form a poly-valent vaccine construct. The chimeric vaccine construct was undergone by molecular modelling, further refinement and energy minimization. We predicted positive results of the vaccine construct in immune simulations with significantly high levels of immune cells. The protein-protein docking analysis of vaccine construct with toll-like receptors predicted efficient binding, which was further validated by molecular dynamics simulation of vaccine construct with TLR-2 and TLR-4 at 120 ns, resulting in stable complexes’ conformation throughout the simulation run. Overall, the vaccine construct demonstrated positive antigenic response. In future, this chimeric vaccine construct or the identified epitopes could be experimentally validated for the development of UPEC vaccines against UTIs. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.24270919
title: Design, one-pot synthesis, computational and biological evaluation of diaryl benzimidazole derivatives as MEK inhibitors

description: MEK mutations are more common in various human malignancies, such as pancreatic cancer (70–90%), mock melanoma (50%), liver cancer (20–40%), colorectal cancer (25–35%), melanoma (15–20%), non-small cell lung cancer (10–20%) and basal breast cancer (1–5%). Considering the significance of MEK mutations in diverse cancer types, the rational design of the proposed compounds relies on the structural resemblance to FDA-approved MEK inhibitors like selumetinib and binimetinib. The compound under design features distinct substitutions at the benzimidazole moiety, specifically at positions 2 and 3, akin to the FDA-approved drugs, albeit differing in positions 5 and 6. Subsequent structural refinement was guided by key elements including the DFG motif, hydrophobic pocket and catalytic loop of the MEK protein. A set of 15 diverse diaryl benzimidazole derivatives (S1–S15) were synthesized <i>via</i> a one-pot approach and characterized through spectroscopic techniques, including MASS, IR, <sup>1</sup>H NMR and <sup>13</sup>C NMR. <i>In vitro</i> anticancer activities of all the synthesized compounds were evaluated against four cancer cell lines, A375, HT −29, A431 and HFF, along with the standard drug trametinib. Molecular docking was performed for all synthesized compounds (S1–15), followed by 950 ns molecular dynamics simulation studies for the promising compounds S1, S5 and S15. The stability of these complexes was assessed by calculating the root-mean-square deviation, solvent accessible surface area and gyration radius relative to their parent structures. Additionally, free energy of binding calculations were performed. Based on the biological and computational results, S15 was the most potent compound and S1 and S5 are comparable to the standard drug trametinib. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.24270919.v1
title: Design, one-pot synthesis, computational and biological evaluation of diaryl benzimidazole derivatives as MEK inhibitors

description: MEK mutations are more common in various human malignancies, such as pancreatic cancer (70–90%), mock melanoma (50%), liver cancer (20–40%), colorectal cancer (25–35%), melanoma (15–20%), non-small cell lung cancer (10–20%) and basal breast cancer (1–5%). Considering the significance of MEK mutations in diverse cancer types, the rational design of the proposed compounds relies on the structural resemblance to FDA-approved MEK inhibitors like selumetinib and binimetinib. The compound under design features distinct substitutions at the benzimidazole moiety, specifically at positions 2 and 3, akin to the FDA-approved drugs, albeit differing in positions 5 and 6. Subsequent structural refinement was guided by key elements including the DFG motif, hydrophobic pocket and catalytic loop of the MEK protein. A set of 15 diverse diaryl benzimidazole derivatives (S1–S15) were synthesized <i>via</i> a one-pot approach and characterized through spectroscopic techniques, including MASS, IR, <sup>1</sup>H NMR and <sup>13</sup>C NMR. <i>In vitro</i> anticancer activities of all the synthesized compounds were evaluated against four cancer cell lines, A375, HT −29, A431 and HFF, along with the standard drug trametinib. Molecular docking was performed for all synthesized compounds (S1–15), followed by 950 ns molecular dynamics simulation studies for the promising compounds S1, S5 and S15. The stability of these complexes was assessed by calculating the root-mean-square deviation, solvent accessible surface area and gyration radius relative to their parent structures. Additionally, free energy of binding calculations were performed. Based on the biological and computational results, S15 was the most potent compound and S1 and S5 are comparable to the standard drug trametinib. Communicated by Ramaswamy H. Sarma
DOI: 10.15468/dl.4vytqy
title: Occurrence Download

description: A dataset listing the 4025 species recorded in GBIF matching the query:
{
 "and" : [
 "HasCoordinate is true",
 "HasGeospatialIssue is false",
 "OccurrenceStatus is Present",
 "TaxonKey is Culicidae"
 ]
}

 The dataset's 4025 records were derived from 948 constituent datasets; see https://api.gbif.org/v1/occurrence/download/0014281-241107131044228/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.24204402
title: Investigation of the anti-cancer potential of epoxyazadiradione in neuroblastoma: experimental assays and molecular analysis

description: Neuroblastoma, the most common childhood solid tumor, originates from primitive sympathetic nervous system cells. Epoxyazadiradione (EAD) is a limonoid derived from <i>Azadirachta indica</i>, belonging to the family Meliaceae. In this study, we isolated the EAD from <i>Azadirachta indica</i> seed and studied the anti-cancer potential against neuroblastoma. Herein, EAD demonstrated significant efficacy against neuroblastoma by suppressing cell proliferation, enhancing the rate of apoptosis and cycle arrest at the SubG<sub>0</sub> and G<sub>2</sub>/M phases. EAD enhanced the pro-apoptotic Caspase 3 and Caspase 9 and inhibited the NF-kβ translocation in a dose-dependent manner. In order to identify the specific EAD target, a gel-free quantitative proteomics study on SH-SY5Y cells using Liquid Chromatography with tandem mass spectrometry was done in a dose-dependent manner, followed by detailed bioinformatics analysis to identify effects on protein. Proteomics data identified that Enolase1 and HSP90 were up-regulated in neuroblastoma. EAD inhibited the expression of Enolase1 and HSP90, validated by mRNA expression, immunoblotting, Enolase1 and HSP90 kit and flow-cytometry based bioassay. Molecular docking study, Molecular dynamic simulation, and along with molecular mechanics/Poisson-Boltzmann surface area analysis also suggested that EAD binds at the active site of the proteins and were stable throughout the 100 ns Molecular dynamic simulation study. Overall, this study suggested EAD exhibited anti-cancer activity against neuroblastoma by targeting Enolase1 and HSP90 pathways. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.24204402.v1
title: Investigation of the anti-cancer potential of epoxyazadiradione in neuroblastoma: experimental assays and molecular analysis

description: Neuroblastoma, the most common childhood solid tumor, originates from primitive sympathetic nervous system cells. Epoxyazadiradione (EAD) is a limonoid derived from <i>Azadirachta indica</i>, belonging to the family Meliaceae. In this study, we isolated the EAD from <i>Azadirachta indica</i> seed and studied the anti-cancer potential against neuroblastoma. Herein, EAD demonstrated significant efficacy against neuroblastoma by suppressing cell proliferation, enhancing the rate of apoptosis and cycle arrest at the SubG<sub>0</sub> and G<sub>2</sub>/M phases. EAD enhanced the pro-apoptotic Caspase 3 and Caspase 9 and inhibited the NF-kβ translocation in a dose-dependent manner. In order to identify the specific EAD target, a gel-free quantitative proteomics study on SH-SY5Y cells using Liquid Chromatography with tandem mass spectrometry was done in a dose-dependent manner, followed by detailed bioinformatics analysis to identify effects on protein. Proteomics data identified that Enolase1 and HSP90 were up-regulated in neuroblastoma. EAD inhibited the expression of Enolase1 and HSP90, validated by mRNA expression, immunoblotting, Enolase1 and HSP90 kit and flow-cytometry based bioassay. Molecular docking study, Molecular dynamic simulation, and along with molecular mechanics/Poisson-Boltzmann surface area analysis also suggested that EAD binds at the active site of the proteins and were stable throughout the 100 ns Molecular dynamic simulation study. Overall, this study suggested EAD exhibited anti-cancer activity against neuroblastoma by targeting Enolase1 and HSP90 pathways. Communicated by Ramaswamy H. Sarma
DOI: 10.15468/dl.4epug8
title: Occurrence Download

description: A dataset containing 7708 species occurrences available in GBIF matching the query:
{
 "and" : [
 "HasCoordinate is true",
 "HasGeospatialIssue is false",
 "TaxonKey is Syngnathus acus Linnaeus, 1758"
 ]
}

 The dataset includes 7708 records from 169 constituent datasets; see https://api.gbif.org/v1/occurrence/download/0014301-241107131044228/datasets/export for details.
 
Data from some individual datasets included in this download may be licensed under less restrictive terms.
DOI: 10.17630/3a553e5b-d66b-4952-a1f5-2869d17a2418
title: Metal oxide vs Organic semiconductor Charge Extraction Layers for Halide Perovskite Indoor Photovoltaics (dataset)
DOI: 10.15468/dl.3vxhdp
title: Occurrence Download

description: A dataset containing 21 species occurrences available in GBIF matching the query:
{
 "and" : [
 "Country is China",
 "HasCoordinate is true",
 "HasGeospatialIssue is false",
 "TaxonKey is Ovis ammon (Linnaeus, 1758)"
 ]
}

 The dataset includes 21 records from 7 constituent datasets; see https://api.gbif.org/v1/occurrence/download/0014303-241107131044228/datasets/export for details.
 
Data from some individual datasets included in this download may be licensed under less restrictive terms.
DOI: 10.15468/dl.nfde7m
title: Occurrence Download

description: A dataset containing 35325 species occurrences available in GBIF matching the query:
{
 "and" : [
 "BasisOfRecord is Specimen",
 "Continent is Asia",
 "HasCoordinate is true",
 "HasGeospatialIssue is false",
 "TaxonKey is Theaceae"
 ]
}

 The dataset includes 35325 records from 133 constituent datasets; see https://api.gbif.org/v1/occurrence/download/0014302-241107131044228/datasets/export for details.
 
Data from some individual datasets included in this download may be licensed under less restrictive terms.