cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.28184678.v1
title: Materials for "Expansion of the tmRNA sequence database and new tools for search and visualization"

description: Database of unique tmRNA sequences. Columns:Unique IDGene formGene segments and their positions on the segmentsEncoded proteolytic tag sequenceGenetic code used for tag translation (https://en.wikipedia.org/wiki/List_of_genetic_codes)Comma-separated scores from Aragorn v1.2.40 and the CMs alpha_tmRNA, beta_tmRNA, cyano_tmRNA, permuted_tmRNA, mt-tmRNA, tmRNA, tmRNA_standard, tmRNA_intronTaxonomy (for prokaryotes, from GTDB release 214)Gene sequence with lower case marking tag CDS, intervening sequence (IVS), and bases corresponding to CCA tailCount of known instances of this sequenceKnown instances ([assembly ID for prokaryotes/]GenBank accession/coordinates)Search phase (see Methods)Note
DOI: 10.6084/m9.figshare.24845106
title: Identifying multi-target drugs for prostate cancer using machine learning-assisted transcriptomic analysis

description: Prostate cancer is a leading cause of cancer death in men, and the development of effective treatments is of great importance. This study explored to identify the candidate drugs for prostate cancer by transcriptomic data and CMap database analysis. After integrating the results of omics analysis, bisoprolol is confirmed as a promising drug. Moreover, cell experiment reveals its potential inhibitory effect on the proliferation of prostate cancer cells. Importantly, machine learning methods are employed to predict the targets of bisoprolol, and the dual-target ADRB3 and hERG are explored by dynamic simulation. The findings of this study demonstrate the potential of bisoprolol as a multi-target drug for prostate cancer treatment and the feasibility of using beta-adrenergic receptor inhibitors in prostate cancer treatment. In addition, the proposed research approach is promising for discovering potential drugs for cancer treatment by leveraging the concept of drug side effects leading to anticancer effects. Further research is necessary to investigate the pharmacological action, potential toxicity, and underlying mechanisms of bisoprolol in treating prostate cancer with ADRB3.
DOI: 10.6084/m9.figshare.24845106.v1
title: Identifying multi-target drugs for prostate cancer using machine learning-assisted transcriptomic analysis

description: Prostate cancer is a leading cause of cancer death in men, and the development of effective treatments is of great importance. This study explored to identify the candidate drugs for prostate cancer by transcriptomic data and CMap database analysis. After integrating the results of omics analysis, bisoprolol is confirmed as a promising drug. Moreover, cell experiment reveals its potential inhibitory effect on the proliferation of prostate cancer cells. Importantly, machine learning methods are employed to predict the targets of bisoprolol, and the dual-target ADRB3 and hERG are explored by dynamic simulation. The findings of this study demonstrate the potential of bisoprolol as a multi-target drug for prostate cancer treatment and the feasibility of using beta-adrenergic receptor inhibitors in prostate cancer treatment. In addition, the proposed research approach is promising for discovering potential drugs for cancer treatment by leveraging the concept of drug side effects leading to anticancer effects. Further research is necessary to investigate the pharmacological action, potential toxicity, and underlying mechanisms of bisoprolol in treating prostate cancer with ADRB3.
DOI: 10.6084/m9.figshare.24851695
title: Uncovering the structural stability of <i>Magnaporthe oryzae</i> effectors: a secretome-wide <i>in silico</i> analysis

description: Rice blast, caused by the ascomycete fungus <i>Magnaporthe oryzae,</i> is a deadly disease and a major threat to global food security. The pathogen secretes small proteinaceous effectors, virulence factors, inside the host to manipulate and perturb the host immune system, allowing the pathogen to colonize and establish a successful infection. While the molecular functions of several effectors are characterized, very little is known about the structural stability of these effectors. We analyzed a total of 554 small secretory proteins (SSPs) from the <i>M. oryzae</i> secretome to decipher key features of intrinsic disorder (ID) and the structural dynamics of the selected putative effectors through thorough and systematic <i>in silico</i> studies. Our results suggest that out of the total SSPs, 66% were predicted as effector proteins, released either into the apoplast or cytoplasm of the host cell. Of these, 68% were found to be intrinsically disordered effector proteins (IDEPs). Among the six distinct classes of disordered effectors, we observed peculiar relationships between the localization of several effectors in the apoplast or cytoplasm and the degree of disorder. We determined the degree of structural disorder and its impact on protein foldability across all the putative small secretory effector proteins from the blast pathogen, further validated by molecular dynamics simulation studies. This study provides definite clues toward unraveling the mystery behind the importance of structural distortions in effectors and their impact on plant-pathogen interactions. The study of these dynamical segments may help identify new effectors as well. Explored secretome of <i>M. oryzae</i> for intrinsic disorder in effectorsClassified intrinsic disorder into six categoriesNoted varying degrees of disorder in apoplastic vs. cytoplasmic effectorsFound a correlation between intrinsic disorder and flexibilityDemonstrated flexibility patterns through molecular dynamics simulationsRevealed that intrinsic disorder influences effector interactionsIdentified an exceptional 100% disordered effector defying observed trends Explored secretome of <i>M. oryzae</i> for intrinsic disorder in effectors Classified intrinsic disorder into six categories Noted varying degrees of disorder in apoplastic vs. cytoplasmic effectors Found a correlation between intrinsic disorder and flexibility Demonstrated flexibility patterns through molecular dynamics simulations Revealed that intrinsic disorder influences effector interactions Identified an exceptional 100% disordered effector defying observed trends
DOI: 10.6084/m9.figshare.24851695.v1
title: Uncovering the structural stability of <i>Magnaporthe oryzae</i> effectors: a secretome-wide <i>in silico</i> analysis

description: Rice blast, caused by the ascomycete fungus <i>Magnaporthe oryzae,</i> is a deadly disease and a major threat to global food security. The pathogen secretes small proteinaceous effectors, virulence factors, inside the host to manipulate and perturb the host immune system, allowing the pathogen to colonize and establish a successful infection. While the molecular functions of several effectors are characterized, very little is known about the structural stability of these effectors. We analyzed a total of 554 small secretory proteins (SSPs) from the <i>M. oryzae</i> secretome to decipher key features of intrinsic disorder (ID) and the structural dynamics of the selected putative effectors through thorough and systematic <i>in silico</i> studies. Our results suggest that out of the total SSPs, 66% were predicted as effector proteins, released either into the apoplast or cytoplasm of the host cell. Of these, 68% were found to be intrinsically disordered effector proteins (IDEPs). Among the six distinct classes of disordered effectors, we observed peculiar relationships between the localization of several effectors in the apoplast or cytoplasm and the degree of disorder. We determined the degree of structural disorder and its impact on protein foldability across all the putative small secretory effector proteins from the blast pathogen, further validated by molecular dynamics simulation studies. This study provides definite clues toward unraveling the mystery behind the importance of structural distortions in effectors and their impact on plant-pathogen interactions. The study of these dynamical segments may help identify new effectors as well. Explored secretome of <i>M. oryzae</i> for intrinsic disorder in effectorsClassified intrinsic disorder into six categoriesNoted varying degrees of disorder in apoplastic vs. cytoplasmic effectorsFound a correlation between intrinsic disorder and flexibilityDemonstrated flexibility patterns through molecular dynamics simulationsRevealed that intrinsic disorder influences effector interactionsIdentified an exceptional 100% disordered effector defying observed trends Explored secretome of <i>M. oryzae</i> for intrinsic disorder in effectors Classified intrinsic disorder into six categories Noted varying degrees of disorder in apoplastic vs. cytoplasmic effectors Found a correlation between intrinsic disorder and flexibility Demonstrated flexibility patterns through molecular dynamics simulations Revealed that intrinsic disorder influences effector interactions Identified an exceptional 100% disordered effector defying observed trends
DOI: 10.6084/m9.figshare.24799615
title: Decoding the therapeutic landscape of alpha-linolenic acid: a network pharmacology and bioinformatics investigation against cancer-related epigenetic modifiers

description: Omega-3 (<i>n</i> − 3) and omega-6 (<i>n</i> − 6) polyunsaturated fatty acids (PUFAs) are vital for human health, but an imbalance between these types is associated with chronic diseases, including cancer. Alpha-linolenic acid (ALA), a <i>n</i> − 3 PUFA, shows promise as an anticancer agent in both laboratory and animal studies. However, the precise molecular mechanisms underlying ALA’s actions against cancer-related epigenetic modifiers (CaEpM) remain unclear. To understand this, we employed network pharmacology (NP) and molecular docking techniques. Our study identified 51 potential ALA targets and GO and KEGG pathway analysis revealed possible molecular targets and signaling pathways of ALA against CaEpM. From PPI analysis, EZH2, KAT2B, SIRT1, KAT2A, KDM6B, EHMT2, WDR5, SETD7, SIRT2, and HDAC3 emerged as the top 10 potential targets. Additionally, GeneMANIA functional association (GMFA) network analysis of these top 10 targets was performed to enhance NP insights and explore ALA’s multi-target approach. After an exhaustive analysis of the core FGN subnetwork, it became evident that 9 out of the 15 targets—namely EZH2, SUZ12, EED, PARP1, HDAC3, DNMT1, NCOR2, KAT2B, and TRRAP—manifested evidently strong and abundant interconnections among each other. Molecular docking of both top 10 targets and core FGN targets confirmed strong binding affinity between ALA and SIRT2, WDR5, KDM6B, EHMT2, HDAC3, EZH2, PARP1, and KAT2B, underscoring their roles in ALA’s anti-CaEpM mechanism. Our findings suggest that ALA may target key signaling pathways related to transcriptional regulation, microRNA involvement, stem cell pluripotency and cellular senescence in cancer epigenetics. These findings illuminate ALA’s potential as a multi-target agent against CaEpM.
DOI: 10.6084/m9.figshare.24799615.v1
title: Decoding the therapeutic landscape of alpha-linolenic acid: a network pharmacology and bioinformatics investigation against cancer-related epigenetic modifiers

description: Omega-3 (<i>n</i> − 3) and omega-6 (<i>n</i> − 6) polyunsaturated fatty acids (PUFAs) are vital for human health, but an imbalance between these types is associated with chronic diseases, including cancer. Alpha-linolenic acid (ALA), a <i>n</i> − 3 PUFA, shows promise as an anticancer agent in both laboratory and animal studies. However, the precise molecular mechanisms underlying ALA’s actions against cancer-related epigenetic modifiers (CaEpM) remain unclear. To understand this, we employed network pharmacology (NP) and molecular docking techniques. Our study identified 51 potential ALA targets and GO and KEGG pathway analysis revealed possible molecular targets and signaling pathways of ALA against CaEpM. From PPI analysis, EZH2, KAT2B, SIRT1, KAT2A, KDM6B, EHMT2, WDR5, SETD7, SIRT2, and HDAC3 emerged as the top 10 potential targets. Additionally, GeneMANIA functional association (GMFA) network analysis of these top 10 targets was performed to enhance NP insights and explore ALA’s multi-target approach. After an exhaustive analysis of the core FGN subnetwork, it became evident that 9 out of the 15 targets—namely EZH2, SUZ12, EED, PARP1, HDAC3, DNMT1, NCOR2, KAT2B, and TRRAP—manifested evidently strong and abundant interconnections among each other. Molecular docking of both top 10 targets and core FGN targets confirmed strong binding affinity between ALA and SIRT2, WDR5, KDM6B, EHMT2, HDAC3, EZH2, PARP1, and KAT2B, underscoring their roles in ALA’s anti-CaEpM mechanism. Our findings suggest that ALA may target key signaling pathways related to transcriptional regulation, microRNA involvement, stem cell pluripotency and cellular senescence in cancer epigenetics. These findings illuminate ALA’s potential as a multi-target agent against CaEpM.
DOI: 10.6084/m9.figshare.24885041
title: Comprehensive mapping of mutations in TDP-43 and α-Synuclein that affect stability and binding

description: Abnormal aggregation and amyloid inclusions of TAR DNA-binding protein 43 (TDP-43) and α-Synuclein (α-Syn) are frequently co-observed in amyotrophic lateral sclerosis, Parkinson’s disease, and Alzheimer’s disease. Several reports showed TDP-43 C-terminal domain (CTD) and α-Syn interact with each other and the aggregates of these two proteins colocalized together in different cellular and animal models. Molecular dynamics simulation was conducted to elucidate the stability of the TDP-43 and Syn complex structure. The interfacial mutations in protein complexes changes the stability and binding affinity of the protein that may cause diseases. Here, we have utilized the computational saturation mutagenesis approach including structure-based stability and binding energy calculations to compute the systemic effects of missense mutations of TDP-43 CTD and α-Syn on protein stability and binding affinity. Most of the interfacial mutations of CTD and α-Syn were found to destabilize the protein and reduced the protein binding affinity. The results thus shed light on the functional consequences of missense mutations observed in TDP-43 associated proteinopathies and may provide the mechanisms of co-morbidities involving these two proteins.
DOI: 10.6084/m9.figshare.24885041.v2
title: Comprehensive mapping of mutations in TDP-43 and α-Synuclein that affect stability and binding

description: Abnormal aggregation and amyloid inclusions of TAR DNA-binding protein 43 (TDP-43) and α-Synuclein (α-Syn) are frequently co-observed in amyotrophic lateral sclerosis, Parkinson’s disease, and Alzheimer’s disease. Several reports showed TDP-43 C-terminal domain (CTD) and α-Syn interact with each other and the aggregates of these two proteins colocalized together in different cellular and animal models. Molecular dynamics simulation was conducted to elucidate the stability of the TDP-43 and Syn complex structure. The interfacial mutations in protein complexes changes the stability and binding affinity of the protein that may cause diseases. Here, we have utilized the computational saturation mutagenesis approach including structure-based stability and binding energy calculations to compute the systemic effects of missense mutations of TDP-43 CTD and α-Syn on protein stability and binding affinity. Most of the interfacial mutations of CTD and α-Syn were found to destabilize the protein and reduced the protein binding affinity. The results thus shed light on the functional consequences of missense mutations observed in TDP-43 associated proteinopathies and may provide the mechanisms of co-morbidities involving these two proteins.
DOI: 10.6084/m9.figshare.24885041.v1
title: Comprehensive mapping of mutations in TDP-43 and α-Synuclein that affect stability and binding

description: Abnormal aggregation and amyloid inclusions of TAR DNA-binding protein 43 (TDP-43) and α-Synuclein (α-Syn) are frequently co-observed in amyotrophic lateral sclerosis, Parkinson’s disease, and Alzheimer’s disease. Several reports showed TDP-43 C-terminal domain (CTD) and α-Syn interact with each other and the aggregates of these two proteins colocalized together in different cellular and animal models. Molecular dynamics simulation was conducted to elucidate the stability of the TDP-43 and Syn complex structure. The interfacial mutations in protein complexes changes the stability and binding affinity of the protein that may cause diseases. Here, we have utilized the computational saturation mutagenesis approach including structure-based stability and binding energy calculations to compute the systemic effects of missense mutations of TDP-43 CTD and α-Syn on protein stability and binding affinity. Most of the interfacial mutations of CTD and α-Syn were found to destabilize the protein and reduced the protein binding affinity. The results thus shed light on the functional consequences of missense mutations observed in TDP-43 associated proteinopathies and may provide the mechanisms of co-morbidities involving these two proteins. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.28129696
title: Organotin(IV) derivatives of 4-chloro-2-methylphenoxyacetic acid: synthesis, spectral characterization, X-ray structures, anticancer, enzyme inhibition, antileishmanial, antimicrobial and antioxidant activities

description: Four organotin(IV) carboxylate complexes; (C<sub>4</sub>H<sub>9</sub>)<sub>3</sub>SnL (<b>1</b>), CH<sub>3</sub>SnL (<b>2</b>), (C<sub>4</sub>H<sub>9</sub>)<sub>2</sub>SnL<sub>2</sub> (<b>3</b>) and (CH<sub>3</sub>)<sub>2</sub>SnL<sub>2</sub> (<b>4</b>) are synthesized by the condensation reaction of organotin(IV) chlorides with sodium-4-chloro-2-methylphenoxyacetate (<b>NaL</b>). The FT-IR spectra suggested bridging/chelating bidentate coordination of the ligand to the tin atom. Single-crystal XRD analysis authenticated the FT-IR findings for <b>1</b> and <b>2</b>. The NMR study has shown no significant differences in the signals of the free and coordinated ligand except for absence of a proton and up-filed/down-field shift of the C signal of the carboxyl group in the spectra. Complexes <b>1</b>–<b>4</b> have shown better enzyme inhibition, antioxidant, antimicrobial, and anticancer activities compared to the free ligand acid. Complex <b>3</b> was the most active inhibitor of AChE, BChE, α-glucosidase and α-amylase with IC<sub>50</sub> values of 43.76, 102.39, 232.71 and 91.84 µg/mL, respectively. Additionally, <b>3</b> with IC<sub>50</sub> values of 7.52 and 8.77 µg/mL in the DPPH and ABTS assays, respectively was better antioxidant than the standard. Complex <b>4</b> was the most efficient inhibitor of MAO-B and COX-2 enzymes with IC<sub>50</sub> values of 106.99 and 12.98 µg/mL, respectively, while <b>1</b> (IC<sub>50</sub> = 38.97 µg/mL) has shown the highest 5-LOX inhibition potential. Complexes <b>1</b>–<b>4</b> with IC<sub>50</sub> values in the range 237.51–168.35 µg/mL have shown better antileishmanial activity than <b>HL</b> (IC<sub>50</sub> = 277.57 µg/mL). The compounds showed good to potent antiproliferative activity in malignant glioma U87 cells with IC<sub>50</sub> values in the range 12.54 ± 0.05 to 37.65 ± 0.04 µg/mL. Antimicrobial activities have shown promising results for the compounds compared to the standards in some cases.
DOI: 10.6084/m9.figshare.28129696.v1
title: Organotin(IV) derivatives of 4-chloro-2-methylphenoxyacetic acid: synthesis, spectral characterization, X-ray structures, anticancer, enzyme inhibition, antileishmanial, antimicrobial and antioxidant activities

description: Four organotin(IV) carboxylate complexes; (C<sub>4</sub>H<sub>9</sub>)<sub>3</sub>SnL (<b>1</b>), CH<sub>3</sub>SnL (<b>2</b>), (C<sub>4</sub>H<sub>9</sub>)<sub>2</sub>SnL<sub>2</sub> (<b>3</b>) and (CH<sub>3</sub>)<sub>2</sub>SnL<sub>2</sub> (<b>4</b>) are synthesized by the condensation reaction of organotin(IV) chlorides with sodium-4-chloro-2-methylphenoxyacetate (<b>NaL</b>). The FT-IR spectra suggested bridging/chelating bidentate coordination of the ligand to the tin atom. Single-crystal XRD analysis authenticated the FT-IR findings for <b>1</b> and <b>2</b>. The NMR study has shown no significant differences in the signals of the free and coordinated ligand except for absence of a proton and up-filed/down-field shift of the C signal of the carboxyl group in the spectra. Complexes <b>1</b>–<b>4</b> have shown better enzyme inhibition, antioxidant, antimicrobial, and anticancer activities compared to the free ligand acid. Complex <b>3</b> was the most active inhibitor of AChE, BChE, α-glucosidase and α-amylase with IC<sub>50</sub> values of 43.76, 102.39, 232.71 and 91.84 µg/mL, respectively. Additionally, <b>3</b> with IC<sub>50</sub> values of 7.52 and 8.77 µg/mL in the DPPH and ABTS assays, respectively was better antioxidant than the standard. Complex <b>4</b> was the most efficient inhibitor of MAO-B and COX-2 enzymes with IC<sub>50</sub> values of 106.99 and 12.98 µg/mL, respectively, while <b>1</b> (IC<sub>50</sub> = 38.97 µg/mL) has shown the highest 5-LOX inhibition potential. Complexes <b>1</b>–<b>4</b> with IC<sub>50</sub> values in the range 237.51–168.35 µg/mL have shown better antileishmanial activity than <b>HL</b> (IC<sub>50</sub> = 277.57 µg/mL). The compounds showed good to potent antiproliferative activity in malignant glioma U87 cells with IC<sub>50</sub> values in the range 12.54 ± 0.05 to 37.65 ± 0.04 µg/mL. Antimicrobial activities have shown promising results for the compounds compared to the standards in some cases.
DOI: 10.6084/m9.figshare.24866220
title: Design of a multi-epitope vaccine (vme-VAC/MST-1) against cholera and vibriosis based on reverse vaccinology and immunoinformatics approaches

description: Vibriosis and cholera are serious diseases distributed worldwide and caused by six marine bacteria of the <i>Vibrio</i> genus. Thousands of deaths occur each year due to these illnesses, necessitating the development of new preventive measures. Presently, the existing cholera vaccine demonstrates an effectiveness of approximately 60%. Here we describe a new multi-epitope vaccine, ‘vme-VAC/MST-1’ based on vaccine targets identified by reverse vaccinology and epitopes predicted by immunoinformatics, two currently effective tools for predicting new vaccines for bacterial pathogens. The vaccine was designed to combat vibriosis and cholera by incorporating epitopes predicted for CTL, HTL, and B cells. These epitopes were identified from six vaccine targets revealed through subtractive genomics, combined with reverse vaccinology, and were further filtered using immunoinformatics approaches based on their predicted immunogenicity. To construct the vaccine, 28 epitopes (24 CTL/B and 4 HTL/B) were linked to the sequence of the cholera toxin B subunit adjuvant<i>. In silico</i> analyses indicate that the resulting immunogen is stable, soluble, non-toxic, and non-allergenic. Furthermore, it exhibits no homology to the host and demonstrates a strong capacity to elicit innate, B-cell, and T-cell immune responses. Our analysis suggests that it is likely to elicit immune reactions mediated through the TLR5 pathway, as evidenced by the molecular docking of the vaccine with the receptor, which revealed high affinity and a favorable reaction. Thus, vme-VAC/MST-1 is predicted to be a safe and effective solution against pathogenic <i>Vibrio</i> spp. However, further experimental analyses are required to measure the vaccine’s effects <i>In vivo.</i>