cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.21864693
title: AlteQ: a new complementarity principle-centered method for the evaluation of docking poses

description: Molecular docking is the most popular and widely used method for identifying novel molecules against a target of interest. However, docking procedures and their validation are still under intense development. In the present investigation, we evaluate a quantum free-orbital AlteQ method for evaluating docking complexes generated by taking EGFR complexes as an example. The AlteQ method calculates the electron density using Slater’s type atomic contributions in the interspace between the receptor and the ligand. Since the interactions are determined by the overlap of electron clouds, they follow the complementarity principle, and an equation can be obtained that describes these interactions. The AlteQ method evaluates the quality of the interaction between the receptor and the ligand, how complementary the interactions are, and due to this, it is used to reject less realistic structures obtained by docking methods. Here, three different equations were used to determine the quality of the interactions in experimental complexes and docked complexes obtained using AutoDock Vina and AutoDock 4.2.6. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.21864693.v1
title: AlteQ: a new complementarity principle-centered method for the evaluation of docking poses

description: Molecular docking is the most popular and widely used method for identifying novel molecules against a target of interest. However, docking procedures and their validation are still under intense development. In the present investigation, we evaluate a quantum free-orbital AlteQ method for evaluating docking complexes generated by taking EGFR complexes as an example. The AlteQ method calculates the electron density using Slater’s type atomic contributions in the interspace between the receptor and the ligand. Since the interactions are determined by the overlap of electron clouds, they follow the complementarity principle, and an equation can be obtained that describes these interactions. The AlteQ method evaluates the quality of the interaction between the receptor and the ligand, how complementary the interactions are, and due to this, it is used to reject less realistic structures obtained by docking methods. Here, three different equations were used to determine the quality of the interactions in experimental complexes and docked complexes obtained using AutoDock Vina and AutoDock 4.2.6. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.22015115
title: HPV and molecular mimicry in systemic lupus erythematosus and an impact of compiling B-cell epitopes and MHC-class II binding profiles with <i>in silico</i> evidence

description: Epidemiological link between HPV and SLE is evolving. The possibility of HPV infection-induced molecular mimicry and systemic lupus erythematosus (SLE) was elucidated through detailed <i>in silico</i> analyses. Conserved regions in the structural protein sequences of high-risk HPV types were inferred, and sequence homologies between viral and human peptides were identified to delineate proteins implicated in SLE. B-cell epitopes and MHC-class II binding were compiled using Immune Epitope Database and ProPred II analysis tool. Molecular modeling and molecular dynamics/simulation (MDS) were performed using AutoDock Vina and GROMACS, respectively. Sequence alignment revealed 32 conserved regions, and 27/32 viral peptides showed varying similarities to human peptides, rich in B-cell epitopes with superior accessibility, high hydrophilicity, antigenicity and disposition to bind many class-II HLA alleles. Molecular docking of 13 viral peptides homologous (100%) to human peptides implicated in SLE showed that VIR-PEP1 (QLFNKPYWL) and VIR-PEP2 (DTYRFVTS) exhibited higher binding affinities than corresponding human peptides to SLE predisposing HLA-DRB1 allele. MDS of these peptides showed that the viral peptides had superior folding, compactness, and a higher number of hydrogen bonds than human peptides throughout the simulation period. SASA analysis revealed that the VIR-PEP1&2 fluctuated less frequently than corresponding human peptides. MM-PBSA revealed that the VIR-PEP2 complex exhibited higher binding energy than the human peptide complex. This suggests that highly conserved structural peptides of high-risk HPV types homologous to human peptides could compete and bind avidly to the HLA allele associated with SLE and predispose HPV-infected individuals to SLE through molecular mimicry. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.22015115.v1
title: HPV and molecular mimicry in systemic lupus erythematosus and an impact of compiling B-cell epitopes and MHC-class II binding profiles with <i>in silico</i> evidence

description: Epidemiological link between HPV and SLE is evolving. The possibility of HPV infection-induced molecular mimicry and systemic lupus erythematosus (SLE) was elucidated through detailed <i>in silico</i> analyses. Conserved regions in the structural protein sequences of high-risk HPV types were inferred, and sequence homologies between viral and human peptides were identified to delineate proteins implicated in SLE. B-cell epitopes and MHC-class II binding were compiled using Immune Epitope Database and ProPred II analysis tool. Molecular modeling and molecular dynamics/simulation (MDS) were performed using AutoDock Vina and GROMACS, respectively. Sequence alignment revealed 32 conserved regions, and 27/32 viral peptides showed varying similarities to human peptides, rich in B-cell epitopes with superior accessibility, high hydrophilicity, antigenicity and disposition to bind many class-II HLA alleles. Molecular docking of 13 viral peptides homologous (100%) to human peptides implicated in SLE showed that VIR-PEP1 (QLFNKPYWL) and VIR-PEP2 (DTYRFVTS) exhibited higher binding affinities than corresponding human peptides to SLE predisposing HLA-DRB1 allele. MDS of these peptides showed that the viral peptides had superior folding, compactness, and a higher number of hydrogen bonds than human peptides throughout the simulation period. SASA analysis revealed that the VIR-PEP1&2 fluctuated less frequently than corresponding human peptides. MM-PBSA revealed that the VIR-PEP2 complex exhibited higher binding energy than the human peptide complex. This suggests that highly conserved structural peptides of high-risk HPV types homologous to human peptides could compete and bind avidly to the HLA allele associated with SLE and predispose HPV-infected individuals to SLE through molecular mimicry. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.22015109
title: Computational modeling of cyanobacterial phytoconstituents against toll-like receptors of skin cancer

description: Melanoma is an extremely dangerous disease. The diagnosis and treatment of it may be difficult because of its diversity and complexity. More than 90% of the marine biomass (microflora and microalgae) constitutes the natural biodiversity reserves. TLR-related research developments indicate possible cancer therapeutic possibilities. In addition to its significant function in innate immunity, TLR activation is connected to the start of pyroptosis, apoptosis, or autophagy in malignance cells. For these reasons, TLR agonists are appealing candidates for the production of cancer medications. From the web databases, the ternary structures of the receptors (TLR3 and TLR4) and ligands are extracted. Sixty-nine compounds were subjected to a drug likeness filter, but only twenty-two were screened further for evaluating ADMET criteria, in which only seven compounds satisfied the pharmacological properties. These compounds are further analyzed for docking parameters against TLRs (TLR3 and TLR4) and molecular simulation investigation of the best cluster to evaluate the complex stability. Molecular docking methodology discovered that Scytonmein has a significant binding potential energy of −5.21 and −7.92 kcal/mol against TLR3 and TLR4, respectively, in comparison to the redock co-crystal structure (−3.98 and −4.30 kcal/mol, respectively). The simulation analysis demonstrates the significant stability of the Scytonemin and TLR4 complexes in terms of average RMSD and RMSF compared to the redock complex, while criteria like solvent-accessible surface area (SASA), gyration (Rg) and hydrogen bonding have further supported the significant interaction and stability of the conformations. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.21821027
title: Bergamottin: location, aggregation and interaction with the plasma membrane

description: Bioactive furanocoumarins, a group of natural secondary metabolites common in higher plants, are recognized for their benefits to human health and have been shown to have numerous biological properties. However, the knowledge of its biomolecular mechanism is not known. One of the main furanocoumarins is bergamottin (BGM), which is characterized by a planar three-ringed structure and a hydrocarbon chain, which give BGM its high lipid/water partition coefficient. Because of that, and although the biological mechanism of BGM is not known, BGM bioactive properties could be ascribed to its potential to interact with the biological membrane, modulating its structure, changing its dynamics and at the same time that it might interact with lipids. For our goal, we have applied molecular dynamics to determine the position of BGM in a complex membrane and discern the possibility of certain interactions with membrane lipids. Our findings establish that BGM tends to locate in the middle of the hydrocarbon layer of the membrane, inserts in between the hydrocarbon chains of the phospholipids in an oblique position with respect to the membrane plane, increasing the fluidity of the membrane. Significantly, BGM tends to be surrounded by POPC molecules but exclude the molecule of CHOL. Outstandingly, BGM molecules associate spontaneously creating aggregates, which does not preclude them from interacting with and inserting into the membrane. The bioactive properties of BGM could be ascribed to its membranotropic effects and support the improvement of these molecules as therapeutic molecules, giving place to new opportunities for potential medical improvements. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.21915216
title: Field and atom-based 3D-QSAR models of chromone (1-benzopyran-4-one) derivatives as MAO inhibitors

description: Monoamine oxidases (MAOs) are flavo-enzymes that aid in the oxidative deamination of neurotransmitters like dopamine, serotonin, and epinephrine. MAO inhibitors are antidepressants that work by preventing the breakdown of brain neurotransmitters and regulating mood. MAO inhibitors that use the chromone (1-benzopyran-4-one) structure have been found to be quite effective in studies. The current study involves the creation of pharmacophore models, 3-D QSAR, virtual screening, and docking investigations, all of which are evaluated using various criteria. The investigation included 39 ligands that emerged pharmacophore AHRRR_1, as the best pharmacophore model with a survival score of 5.6485. The 3D QSAR investigation revealed a significant model with the values of <i>R</i><sup>2</sup> = 0.9064 and <i>Q</i><sup>2</sup> = 0.8239. Docking study revealed that compound 18 had the highest docking (−10.402 kcal/mol) score in the series and showed interactions with the essential amino acid TYR398 required for MAO inhibitory activity. ZINC compounds were screened using the created pharmacophore model, which was followed up with a virtual screening study. The ZINC compounds with the best XP docking scores are ZINC03113255, ZINC07777127, ZINC05166353 and ZINC09341502 (with docking scores −10.021, −9.486, −8.031 and −7.792 kcal/mol, respectively). ZINC03113255, which showed the best score, has binding interactions with amino acid residues, TYR326, TYR398 and LYS296 of monoamine oxidase B. The ADME analysis demonstrated the compound’s drug-like characteristics. The findings of this study may be used in the development of chromone compounds that target the MAO inhibitor. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.21786684
title: Citrus nutraceutical eriocitrin and its metabolites are partial agonists of peroxisome proliferator-activated receptor gamma (PPARγ): a molecular docking and molecular dynamics study

description: Peroxisome proliferator-activated receptor gamma (PPARγ) agonists are potent insulin sensitizers in treating type 2 diabetes. Despite being very effective in the fight against diabetes-mediated complications, PPARγ agonists are accompanied by severe side effects leading to complicated health problems, making the discovery of novel safe ligands highly pertinent. A significant intense research effort is in progress to explore the PPARγ activating potential of a wide range of natural compounds. Lemon (Citrus limon) contains various bioactive flavonoids, and eriocitrin is the major flavonoid. It possesses substantial antioxidant and anticancer, lipid-lowering activities and prevents obesity-associated metabolic diseases. Eriocitrin is metabolized to eriodictyol in the intestine, and the absorbed eriodictyol undergoes conversion to numerous metabolites <i>in vivo</i>. It is unclear if eriocitrin or its metabolites are responsible for their beneficial effects. We have used molecular docking, ADMET properties, drug-likeness score and molecular dynamics simulation study to find if eriocitrin and its metabolites are potent binders for PPARγ. Docking studies revealed that eriocitrin binds to PPARγ with the highest binding energy, but ADMET properties and <i>in vivo</i> studies show that the bioavailability of eriocitrin is very poor. Molecular dynamics studies were carried out to validate the docking results, and multiple parameters like RMSD, RMSF, Radius of gyration, SASA, hydrogen bond analysis, interaction energy, principal component analysis, Gibbs free energy and MM-PBSA were calculated. Based on our studies, eriodictyol, eriodictyol 7-<i>O</i>-glucuronide, eriodictyol 3′-<i>O</i>-glucuronide, homoeriodictyol and homoeriodictyol 7-<i>O</i>-glucuronide which are metabolites of eriocitrin appear to be potent partial agonists of PPARγ under physiological conditions. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.21821027.v1
title: Bergamottin: location, aggregation and interaction with the plasma membrane

description: Bioactive furanocoumarins, a group of natural secondary metabolites common in higher plants, are recognized for their benefits to human health and have been shown to have numerous biological properties. However, the knowledge of its biomolecular mechanism is not known. One of the main furanocoumarins is bergamottin (BGM), which is characterized by a planar three-ringed structure and a hydrocarbon chain, which give BGM its high lipid/water partition coefficient. Because of that, and although the biological mechanism of BGM is not known, BGM bioactive properties could be ascribed to its potential to interact with the biological membrane, modulating its structure, changing its dynamics and at the same time that it might interact with lipids. For our goal, we have applied molecular dynamics to determine the position of BGM in a complex membrane and discern the possibility of certain interactions with membrane lipids. Our findings establish that BGM tends to locate in the middle of the hydrocarbon layer of the membrane, inserts in between the hydrocarbon chains of the phospholipids in an oblique position with respect to the membrane plane, increasing the fluidity of the membrane. Significantly, BGM tends to be surrounded by POPC molecules but exclude the molecule of CHOL. Outstandingly, BGM molecules associate spontaneously creating aggregates, which does not preclude them from interacting with and inserting into the membrane. The bioactive properties of BGM could be ascribed to its membranotropic effects and support the improvement of these molecules as therapeutic molecules, giving place to new opportunities for potential medical improvements. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.21915216.v1
title: Field and atom-based 3D-QSAR models of chromone (1-benzopyran-4-one) derivatives as MAO inhibitors

description: Monoamine oxidases (MAOs) are flavo-enzymes that aid in the oxidative deamination of neurotransmitters like dopamine, serotonin, and epinephrine. MAO inhibitors are antidepressants that work by preventing the breakdown of brain neurotransmitters and regulating mood. MAO inhibitors that use the chromone (1-benzopyran-4-one) structure have been found to be quite effective in studies. The current study involves the creation of pharmacophore models, 3-D QSAR, virtual screening, and docking investigations, all of which are evaluated using various criteria. The investigation included 39 ligands that emerged pharmacophore AHRRR_1, as the best pharmacophore model with a survival score of 5.6485. The 3D QSAR investigation revealed a significant model with the values of <i>R</i><sup>2</sup> = 0.9064 and <i>Q</i><sup>2</sup> = 0.8239. Docking study revealed that compound 18 had the highest docking (−10.402 kcal/mol) score in the series and showed interactions with the essential amino acid TYR398 required for MAO inhibitory activity. ZINC compounds were screened using the created pharmacophore model, which was followed up with a virtual screening study. The ZINC compounds with the best XP docking scores are ZINC03113255, ZINC07777127, ZINC05166353 and ZINC09341502 (with docking scores −10.021, −9.486, −8.031 and −7.792 kcal/mol, respectively). ZINC03113255, which showed the best score, has binding interactions with amino acid residues, TYR326, TYR398 and LYS296 of monoamine oxidase B. The ADME analysis demonstrated the compound’s drug-like characteristics. The findings of this study may be used in the development of chromone compounds that target the MAO inhibitor. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.21940068
title: Molecular cloning, expression, mRNA secondary structure and immunological characterization of mussel foot proteins (Mfps) (Mollusca: Bivalvia)

description: The macroscale production of mussel foot proteins (Mfps) in the expression system has not succeeded to date. The principal reasons for this are low levels of expression and yield of Mfps, lack of post-translational modifications (PTMs), and immunological toxic effects on the host system. Identification of post-translational modification sites, suitable expression hosts, and immunological responses through an experimental approach is very costly and time-consuming. However, in the present study, <i>in silico</i> post-translation modification, antigenicity, allergenicity, and the immunological reaction of all available Mfps were characterized. Furthermore, all Mfps were codon optimized in three different expression systems to determine the best expression host. Finally, we performed the <i>in-silico</i> cloning of all codon-optimized Mfps in a suitable host (<i>E. coli</i> K12, pET28a(+) vector) and analyzed the secondary structure of mRNA and its structural stability. Among the 78 Mfps, six fps are considered potential allergenic proteins, six fps are considered non-allergenic proteins, and all other fps are probably allergenic. High antigenicity was observed in bacterial cells as compared to yeast and tumor cells. Nevertheless, the predicted expression of Mfps in a bacterial host is higher than in other expression hosts. Important to note that all Mfps showed significant immunological activity in the human system, and we concluded that these antigenic, allergenic, and immunological properties are directly correlated with their amino acid composition. The study’s major goal is to provide a comprehensive understanding of Mfps and aid in the future genetic engineering and expression of Mfps and its diverse applications in different fields. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.22015109.v1
title: Computational modeling of cyanobacterial phytoconstituents against toll-like receptors of skin cancer

description: Melanoma is an extremely dangerous disease. The diagnosis and treatment of it may be difficult because of its diversity and complexity. More than 90% of the marine biomass (microflora and microalgae) constitutes the natural biodiversity reserves. TLR-related research developments indicate possible cancer therapeutic possibilities. In addition to its significant function in innate immunity, TLR activation is connected to the start of pyroptosis, apoptosis, or autophagy in malignance cells. For these reasons, TLR agonists are appealing candidates for the production of cancer medications. From the web databases, the ternary structures of the receptors (TLR3 and TLR4) and ligands are extracted. Sixty-nine compounds were subjected to a drug likeness filter, but only twenty-two were screened further for evaluating ADMET criteria, in which only seven compounds satisfied the pharmacological properties. These compounds are further analyzed for docking parameters against TLRs (TLR3 and TLR4) and molecular simulation investigation of the best cluster to evaluate the complex stability. Molecular docking methodology discovered that Scytonmein has a significant binding potential energy of −5.21 and −7.92 kcal/mol against TLR3 and TLR4, respectively, in comparison to the redock co-crystal structure (−3.98 and −4.30 kcal/mol, respectively). The simulation analysis demonstrates the significant stability of the Scytonemin and TLR4 complexes in terms of average RMSD and RMSF compared to the redock complex, while criteria like solvent-accessible surface area (SASA), gyration (Rg) and hydrogen bonding have further supported the significant interaction and stability of the conformations. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.21786684.v1
title: Citrus nutraceutical eriocitrin and its metabolites are partial agonists of peroxisome proliferator-activated receptor gamma (PPARγ): a molecular docking and molecular dynamics study

description: Peroxisome proliferator-activated receptor gamma (PPARγ) agonists are potent insulin sensitizers in treating type 2 diabetes. Despite being very effective in the fight against diabetes-mediated complications, PPARγ agonists are accompanied by severe side effects leading to complicated health problems, making the discovery of novel safe ligands highly pertinent. A significant intense research effort is in progress to explore the PPARγ activating potential of a wide range of natural compounds. Lemon (Citrus limon) contains various bioactive flavonoids, and eriocitrin is the major flavonoid. It possesses substantial antioxidant and anticancer, lipid-lowering activities and prevents obesity-associated metabolic diseases. Eriocitrin is metabolized to eriodictyol in the intestine, and the absorbed eriodictyol undergoes conversion to numerous metabolites <i>in vivo</i>. It is unclear if eriocitrin or its metabolites are responsible for their beneficial effects. We have used molecular docking, ADMET properties, drug-likeness score and molecular dynamics simulation study to find if eriocitrin and its metabolites are potent binders for PPARγ. Docking studies revealed that eriocitrin binds to PPARγ with the highest binding energy, but ADMET properties and <i>in vivo</i> studies show that the bioavailability of eriocitrin is very poor. Molecular dynamics studies were carried out to validate the docking results, and multiple parameters like RMSD, RMSF, Radius of gyration, SASA, hydrogen bond analysis, interaction energy, principal component analysis, Gibbs free energy and MM-PBSA were calculated. Based on our studies, eriodictyol, eriodictyol 7-<i>O</i>-glucuronide, eriodictyol 3′-<i>O</i>-glucuronide, homoeriodictyol and homoeriodictyol 7-<i>O</i>-glucuronide which are metabolites of eriocitrin appear to be potent partial agonists of PPARγ under physiological conditions. Communicated by Ramaswamy H. Sarma