cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.9205376
title: 3D QSAR pharmacophore-based virtual screening for the identification of potential inhibitors of tyrosinase

description: Tyrosinase plays an important role in melanin biosynthesis and protects skin against ultraviolet radiations. Functional deficiency of tyrosinase results in serious dermatological diseases. Tyrosinase also participates in neuromelanin formation in the human brain, which leads to neurodegeneration resulting in Parkinson’s disease. In fruits and vegetables, tyrosinase plays a critical role in senescence, causing undesired browning that results in faster deterioration and shorter shelf lines. The only commercially available tyrosinase is mushroom tyrosinase and it shows the highest homology to the mammalian tyrosinase. Although kojic acid is currently used as a tyrosinase inhibitor, they have serious side effects such as dermatitis, carcinogenesis and hepatotoxicity. Therefore, in order to develop a more active and safer tyrosinase inhibitor, 3D QSAR pharmacophore models were generated based on experimentally known inhibitors. The pharmacophore model, Hypo1, was developed with a large cost difference, high correlation coefficient and low RMS deviation. Hypo1 showed a good spatial arrangement; consisting of five-point features including two hydrogen bond acceptor, one hydrogen bond donor and two hydrophobic features. Hypo1 was further validated by cost analysis, test set and Fisher’s randomisation method. Hypo1 was used as a 3D query for screening the in-house drug-like databases, and the hits were further selected by applying ADMET, Lipinski’s rule of five and fit value criteria. To identify binding conformations, the obtained hits were subjected to molecular docking. Finally, molecular dynamics simulations revealed the appropriate binding modes of hit compounds. To conclude, we propose the final three hit compounds with new structural scaffolds as a virtual candidate as tyrosinase inhibitors. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.9205376.v1
title: 3D QSAR pharmacophore-based virtual screening for the identification of potential inhibitors of tyrosinase

description: Tyrosinase plays an important role in melanin biosynthesis and protects skin against ultraviolet radiations. Functional deficiency of tyrosinase results in serious dermatological diseases. Tyrosinase also participates in neuromelanin formation in the human brain, which leads to neurodegeneration resulting in Parkinson’s disease. In fruits and vegetables, tyrosinase plays a critical role in senescence, causing undesired browning that results in faster deterioration and shorter shelf lines. The only commercially available tyrosinase is mushroom tyrosinase and it shows the highest homology to the mammalian tyrosinase. Although kojic acid is currently used as a tyrosinase inhibitor, they have serious side effects such as dermatitis, carcinogenesis and hepatotoxicity. Therefore, in order to develop a more active and safer tyrosinase inhibitor, 3D QSAR pharmacophore models were generated based on experimentally known inhibitors. The pharmacophore model, Hypo1, was developed with a large cost difference, high correlation coefficient and low RMS deviation. Hypo1 showed a good spatial arrangement; consisting of five-point features including two hydrogen bond acceptor, one hydrogen bond donor and two hydrophobic features. Hypo1 was further validated by cost analysis, test set and Fisher’s randomisation method. Hypo1 was used as a 3D query for screening the in-house drug-like databases, and the hits were further selected by applying ADMET, Lipinski’s rule of five and fit value criteria. To identify binding conformations, the obtained hits were subjected to molecular docking. Finally, molecular dynamics simulations revealed the appropriate binding modes of hit compounds. To conclude, we propose the final three hit compounds with new structural scaffolds as a virtual candidate as tyrosinase inhibitors. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.9724877
title: Computational prediction and experimental validation of the activator function of C2-β-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone on pancreatic and hepatic hexokinase

description: This study identifies and validates hexokinase type 4 (HK4), an isozyme of hexokinase in the liver and pancreas, as an important target of C2-β-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone (βdGT), a xanthone glucoside suggested to have antidiabetic property. In the study, we applied the computational pipeline of molecular docking followed by the molecular dynamics simulations to shortlist potential βdGT protein targets. The analysis of protein dynamics and the binding free energy (Δ<i>G</i>) led us to the identification of HK4 as a key βdGT target, whereby the binding mode and domain dynamics suggested the activator function of βdGT. βdGT bound to the allosteric site of the isozyme ∼13 Å away from the substrate (glucose)-binding site. The binding free energy of the ligand-protein complex was energetically feasible (Δ<i>G</i>, –41.61 kcal/mol) and the cleft angle deviation between the two (small and large) domains of HK4 revealed differential HK4 dynamics in response to βdGT binding. 3D structure analysis of the isozyme-ligand complex highlighted the role of Arg63, Glu67 and Lys458 in ligand stabilization and hydrophobic interactions mediated by Tyr214 and Met235. Experimental validation of the results of computational analysis confirmed the activator function of βdGT on HK4. The study has implication in diabetes as βdGT may be used to lower the blood glucose level by activating hepatic and pancreatic hexokinase without the risk of hypoglycemia. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.9724877.v1
title: Computational prediction and experimental validation of the activator function of C2-β-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone on pancreatic and hepatic hexokinase

description: This study identifies and validates hexokinase type 4 (HK4), an isozyme of hexokinase in the liver and pancreas, as an important target of C2-β-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone (βdGT), a xanthone glucoside suggested to have antidiabetic property. In the study, we applied the computational pipeline of molecular docking followed by the molecular dynamics simulations to shortlist potential βdGT protein targets. The analysis of protein dynamics and the binding free energy (Δ<i>G</i>) led us to the identification of HK4 as a key βdGT target, whereby the binding mode and domain dynamics suggested the activator function of βdGT. βdGT bound to the allosteric site of the isozyme ∼13 Å away from the substrate (glucose)-binding site. The binding free energy of the ligand-protein complex was energetically feasible (Δ<i>G</i>, –41.61 kcal/mol) and the cleft angle deviation between the two (small and large) domains of HK4 revealed differential HK4 dynamics in response to βdGT binding. 3D structure analysis of the isozyme-ligand complex highlighted the role of Arg63, Glu67 and Lys458 in ligand stabilization and hydrophobic interactions mediated by Tyr214 and Met235. Experimental validation of the results of computational analysis confirmed the activator function of βdGT on HK4. The study has implication in diabetes as βdGT may be used to lower the blood glucose level by activating hepatic and pancreatic hexokinase without the risk of hypoglycemia. Communicated by Ramaswamy H. Sarma
DOI: 10.15156/bio/sh1966565.08fu
title: SH1966565.08FU

description: UNITE provides a unified way for delimiting, identifying, communicating, and working with DNA-based Species Hypotheses (SH). All fungal ITS sequences in the international nucleotide sequence databases are clustered to approximately the species level by applying a set of dynamic distance values (<0.5 - 3.0%). All species hypotheses are given a unique, stable name in the form of a DOI, and their taxonomic and ecological annotations are verified through distributed, web-based third-party annotation efforts. SHs are connected to a taxon name and its classification as far as possible (phylum, class, order, etc.) by taking into account identifications for all sequences in the SH. An automatically or manually designated sequence is chosen to represent each such SH. These sequences are released (https://unite.ut.ee/repository.php) for use by the scientific community in, for example, local sequence similarity searches and next-generation sequencing analysis pipelines. The system and the data are updated automatically as the number of public fungal ITS sequences grows.
DOI: 10.15156/bio/sh1966566.08fu
title: SH1966566.08FU

description: UNITE provides a unified way for delimiting, identifying, communicating, and working with DNA-based Species Hypotheses (SH). All fungal ITS sequences in the international nucleotide sequence databases are clustered to approximately the species level by applying a set of dynamic distance values (<0.5 - 3.0%). All species hypotheses are given a unique, stable name in the form of a DOI, and their taxonomic and ecological annotations are verified through distributed, web-based third-party annotation efforts. SHs are connected to a taxon name and its classification as far as possible (phylum, class, order, etc.) by taking into account identifications for all sequences in the SH. An automatically or manually designated sequence is chosen to represent each such SH. These sequences are released (https://unite.ut.ee/repository.php) for use by the scientific community in, for example, local sequence similarity searches and next-generation sequencing analysis pipelines. The system and the data are updated automatically as the number of public fungal ITS sequences grows.
DOI: 10.15156/bio/sh2656979.08fu
title: SH2656979.08FU

description: UNITE provides a unified way for delimiting, identifying, communicating, and working with DNA-based Species Hypotheses (SH). All fungal ITS sequences in the international nucleotide sequence databases are clustered to approximately the species level by applying a set of dynamic distance values (<0.5 - 3.0%). All species hypotheses are given a unique, stable name in the form of a DOI, and their taxonomic and ecological annotations are verified through distributed, web-based third-party annotation efforts. SHs are connected to a taxon name and its classification as far as possible (phylum, class, order, etc.) by taking into account identifications for all sequences in the SH. An automatically or manually designated sequence is chosen to represent each such SH. These sequences are released (https://unite.ut.ee/repository.php) for use by the scientific community in, for example, local sequence similarity searches and next-generation sequencing analysis pipelines. The system and the data are updated automatically as the number of public fungal ITS sequences grows.
DOI: 10.15156/bio/sh2656980.08fu
title: SH2656980.08FU

description: UNITE provides a unified way for delimiting, identifying, communicating, and working with DNA-based Species Hypotheses (SH). All fungal ITS sequences in the international nucleotide sequence databases are clustered to approximately the species level by applying a set of dynamic distance values (<0.5 - 3.0%). All species hypotheses are given a unique, stable name in the form of a DOI, and their taxonomic and ecological annotations are verified through distributed, web-based third-party annotation efforts. SHs are connected to a taxon name and its classification as far as possible (phylum, class, order, etc.) by taking into account identifications for all sequences in the SH. An automatically or manually designated sequence is chosen to represent each such SH. These sequences are released (https://unite.ut.ee/repository.php) for use by the scientific community in, for example, local sequence similarity searches and next-generation sequencing analysis pipelines. The system and the data are updated automatically as the number of public fungal ITS sequences grows.
DOI: 10.6084/m9.figshare.8971079.v3
title: Contriving a chimeric polyvalent vaccine to prevent infections caused by herpes simplex virus (type-1 and type-2): an exploratory immunoinformatic approach

description: Herpes simplex virus type 1 (HSV-1) and 2 (HSV-2) cause a variety of infections including oral-facial infections, genital herpes, herpes keratitis, cutaneous infection and so on. To date, FDA-approved licensed HSV vaccine is not available yet. Hence, the study was conducted to identify and characterize an effective epitope based polyvalent vaccine against both types of Herpes Simplex Virus. The selected proteins were retrieved from ViralZone and assessed to design highly antigenic epitopes by binding analyses of the peptides with MHC class-I and class-II molecules, antigenicity screening, transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis and molecular docking approach. The final vaccine was constructed by the combination of top CTL, HTL and BCL epitopes from each protein along with suitable adjuvant and linkers. Physicochemical and secondary structure analysis, disulfide engineering, molecular dynamic simulation and codon adaptation were further employed to develop a unique multi-epitope peptide vaccine. Docking analysis of the refined vaccine structure with different MHC molecules and human immune TLR-2 receptor demonstrated higher interaction. Complexed structure of the modeled vaccine and TLR-2 showed minimal deformability at molecular level. Moreover, translational potency and microbial expression of the modeled vaccine was analyzed with pET28a(+) vector for <i>E. coli</i> strain K12 and the vaccine constructs had no similarity with entire human proteome. The study enabled design of a novel chimeric polyvalent vaccine to confer broad range immunity against both HSV serotypes. However, further wet lab based research using model animals are highly recommended to experimentally validate our findings. Communicated by Ramaswamy H. Sarma
DOI: 10.15156/bio/sh1966567.08fu
title: SH1966567.08FU

description: UNITE provides a unified way for delimiting, identifying, communicating, and working with DNA-based Species Hypotheses (SH). All fungal ITS sequences in the international nucleotide sequence databases are clustered to approximately the species level by applying a set of dynamic distance values (<0.5 - 3.0%). All species hypotheses are given a unique, stable name in the form of a DOI, and their taxonomic and ecological annotations are verified through distributed, web-based third-party annotation efforts. SHs are connected to a taxon name and its classification as far as possible (phylum, class, order, etc.) by taking into account identifications for all sequences in the SH. An automatically or manually designated sequence is chosen to represent each such SH. These sequences are released (https://unite.ut.ee/repository.php) for use by the scientific community in, for example, local sequence similarity searches and next-generation sequencing analysis pipelines. The system and the data are updated automatically as the number of public fungal ITS sequences grows.
DOI: 10.15156/bio/sh1966568.08fu
title: SH1966568.08FU

description: UNITE provides a unified way for delimiting, identifying, communicating, and working with DNA-based Species Hypotheses (SH). All fungal ITS sequences in the international nucleotide sequence databases are clustered to approximately the species level by applying a set of dynamic distance values (<0.5 - 3.0%). All species hypotheses are given a unique, stable name in the form of a DOI, and their taxonomic and ecological annotations are verified through distributed, web-based third-party annotation efforts. SHs are connected to a taxon name and its classification as far as possible (phylum, class, order, etc.) by taking into account identifications for all sequences in the SH. An automatically or manually designated sequence is chosen to represent each such SH. These sequences are released (https://unite.ut.ee/repository.php) for use by the scientific community in, for example, local sequence similarity searches and next-generation sequencing analysis pipelines. The system and the data are updated automatically as the number of public fungal ITS sequences grows.
DOI: 10.6084/m9.figshare.8971079
title: Contriving a chimeric polyvalent vaccine to prevent infections caused by herpes simplex virus (type-1 and type-2): an exploratory immunoinformatic approach

description: Herpes simplex virus type 1 (HSV-1) and 2 (HSV-2) cause a variety of infections including oral-facial infections, genital herpes, herpes keratitis, cutaneous infection and so on. To date, FDA-approved licensed HSV vaccine is not available yet. Hence, the study was conducted to identify and characterize an effective epitope based polyvalent vaccine against both types of Herpes Simplex Virus. The selected proteins were retrieved from ViralZone and assessed to design highly antigenic epitopes by binding analyses of the peptides with MHC class-I and class-II molecules, antigenicity screening, transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis and molecular docking approach. The final vaccine was constructed by the combination of top CTL, HTL and BCL epitopes from each protein along with suitable adjuvant and linkers. Physicochemical and secondary structure analysis, disulfide engineering, molecular dynamic simulation and codon adaptation were further employed to develop a unique multi-epitope peptide vaccine. Docking analysis of the refined vaccine structure with different MHC molecules and human immune TLR-2 receptor demonstrated higher interaction. Complexed structure of the modeled vaccine and TLR-2 showed minimal deformability at molecular level. Moreover, translational potency and microbial expression of the modeled vaccine was analyzed with pET28a(+) vector for <i>E. coli</i> strain K12 and the vaccine constructs had no similarity with entire human proteome. The study enabled design of a novel chimeric polyvalent vaccine to confer broad range immunity against both HSV serotypes. However, further wet lab based research using model animals are highly recommended to experimentally validate our findings. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.8971079.v2
title: Contriving a chimeric polyvalent vaccine to prevent infections caused by herpes simplex virus (type-1 and type-2): an exploratory immunoinformatic approach

description: Herpes simplex virus type 1 (HSV-1) and 2 (HSV-2) cause a variety of infections including oral-facial infections, genital herpes, herpes keratitis, cutaneous infection and so on. To date, FDA-approved licensed HSV vaccine is not available yet. Hence, the study was conducted to identify and characterize an effective epitope based polyvalent vaccine against both types of Herpes Simplex Virus. The selected proteins were retrieved from ViralZone and assessed to design highly antigenic epitopes by binding analyses of the peptides with MHC class-I and class-II molecules, antigenicity screening, transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis and molecular docking approach. The final vaccine was constructed by the combination of top CTL, HTL and BCL epitopes from each protein along with suitable adjuvant and linkers. Physicochemical and secondary structure analysis, disulfide engineering, molecular dynamic simulation and codon adaptation were further employed to develop a unique multi-epitope peptide vaccine. Docking analysis of the refined vaccine structure with different MHC molecules and human immune TLR-2 receptor demonstrated higher interaction. Complexed structure of the modeled vaccine and TLR-2 showed minimal deformability at molecular level. Moreover, translational potency and microbial expression of the modeled vaccine was analyzed with pET28a(+) vector for <i>E. coli</i> strain K12 and the vaccine constructs had no similarity with entire human proteome. The study enabled design of a novel chimeric polyvalent vaccine to confer broad range immunity against both HSV serotypes. However, further wet lab based research using model animals are highly recommended to experimentally validate our findings. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.9611288
title: Identification potential inhibitors against the <i>Streptococcus</i> quorum-sensing signal pathway

description: Streptococcal infections are common in human and antibiotics are frequently prescribed in clinical practice. However, infections caused by drug-resistant strains are particularly difficult to treat using common antibiotics. Hence, there is an urgent need for new antibiotics. Quorum sensing is a regulatory mechanism involving cell communication that is thought to play an important role in various bacterial infections, including those caused by <i>Streptococcus</i>. The ATP-binding cassette transporter ComA of <i>Streptococcus</i> is essential for quorum-sensing signal production. The inhibition of the ComA peptidase domain (ComA PEP) suppresses the quorum-sensing pathway and resulting changes in phenotype and/or behavior. Using virtual screening and molecular dynamics simulations, two promising candidate compounds, ZINC32918029 and ZINC6751571, were found. These compounds had similar binding modes and interactions to the experimentally determined reference inhibitor 6CH. However, a significantly stronger negative binding energy was achieved (−113.501 ± 15.312 KJ/mol and −103.153 ± 11.912 KJ/mol for ZINC32918029 and ZINC6751571, respectively). Molecular dynamics simulations also revealed that ZINC32918029 and ZINC6751571 had a strong affinity for ComA PEP. These results indicate that ZINC32918029 and ZINC6751571 are promising candidate inhibitors of the <i>Streptococcus</i> quorum-sensing pathway. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.9611288.v1
title: Identification potential inhibitors against the <i>Streptococcus</i> quorum-sensing signal pathway

description: Streptococcal infections are common in human and antibiotics are frequently prescribed in clinical practice. However, infections caused by drug-resistant strains are particularly difficult to treat using common antibiotics. Hence, there is an urgent need for new antibiotics. Quorum sensing is a regulatory mechanism involving cell communication that is thought to play an important role in various bacterial infections, including those caused by <i>Streptococcus</i>. The ATP-binding cassette transporter ComA of <i>Streptococcus</i> is essential for quorum-sensing signal production. The inhibition of the ComA peptidase domain (ComA PEP) suppresses the quorum-sensing pathway and resulting changes in phenotype and/or behavior. Using virtual screening and molecular dynamics simulations, two promising candidate compounds, ZINC32918029 and ZINC6751571, were found. These compounds had similar binding modes and interactions to the experimentally determined reference inhibitor 6CH. However, a significantly stronger negative binding energy was achieved (−113.501 ± 15.312 KJ/mol and −103.153 ± 11.912 KJ/mol for ZINC32918029 and ZINC6751571, respectively). Molecular dynamics simulations also revealed that ZINC32918029 and ZINC6751571 had a strong affinity for ComA PEP. These results indicate that ZINC32918029 and ZINC6751571 are promising candidate inhibitors of the <i>Streptococcus</i> quorum-sensing pathway. Communicated by Ramaswamy H. Sarma