cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.11506434.v2
title: Exploring structural requirements of isoform selective histone deacetylase inhibitors: a comparative <i>in silico</i> study

description: Histone deacetylases (HDACs) are a widely popular class of epigenetic regulators, second only in importance to DNA methyltransferases. They are responsible for deacetylating the lysine residues of a wide range of proteins, both nuclear and cytoplasmic. Therefore, deregulated HDAC activity is implicated in disruption of important biological functions leading to cancerous, neuropathological, infectious and inflammatory diseased states. The current therapeutic strategies aimed at combating HDAC related pathologies consist of pan HDAC inhibitors that target multiple HDAC isoforms. Many side-effects of such therapeutics have been reported due to off-target effects. Hence, efforts need to be focused towards developing therapeutics targeting single isoforms. This work aims at recognizing structural features, both of receptors and inhibitors, that would help achieve selective inhibition of HDAC isoforms. Protein alignment studies have been carried out to define the receptor structure differences that can be exploited for this purpose. Binding modes of highly isoform selective inhibitors have been established through molecular docking studies to characterize the receptor-ligand interactions responsible for selective inhibition. This information is represented with the help of pharmacophore models.
DOI: 10.17188/1689224
title: Materials Data on BaLiCaVP2O9 by Materials Project

description: Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations
DOI: 10.6084/m9.figshare.11864394.v2
title: Effect of periphery cationic substituents of porphyrin on the B-Z transition of poly[d(A-T)<sub>2</sub>], poly[d(G-C)<sub>2</sub>] and their binding modes

description: The binding mode of cationic porphyrin (<i>trans</i>-BMPyP) with poly[d(G-C)<sub>2</sub>] and poly[d(A-T)<sub>2</sub>] was examined according to the site of the periphery cationic methyl pyridine ion of the cationic porphyrin (<i>o-, m-, p-</i>) as well as the possibility of a B-Z transition depending on the binding modes by measuring the absorption spectrum and circular dichroism (CD). The negative band found in the soret region showed the intercalation mode of <i>m-</i> and <i>p-trans-</i>BMPyP-poly[d(G-C)<sub>2</sub>] to the DNA base pairs, but no B-Z transition was induced. On the other hand, the distinctive bisignate band found in the soret region of the CD spectrum for <i>m-</i> and <i>p-trans-</i>BMPyP-poly[d(A-T)<sub>2</sub>] suggests that <i>m-</i> and <i>p-trans-</i>BMPyP have an effective extensive stacking-based binding mode along with the skeleton of poly[d(A-T)<sub>2</sub>], wherein the B-Z transition was induced through extensive stacking. The difference in binding mode was attributed to the difference in the molecular structure depending on the site of the periphery cationic methyl pyridine ion in the cationic porphyrin. In other words, <i>o-trans-</i>BMPyP is nonplanar because of the steric hindrance of the cationic methyl pyridine ion at the <i>o-</i>site. In contrast, <i>m-</i> and <i>p-trans-</i>BMPyP are planar, but not all porphyrins with a planar structure undergo the B-Z transition. In conclusion, a B-Z transition is induced if the structure of a porphyrin is planar and the binding mode allows the porphyrins to be stacked effectively along the DNA skeleton, not in a binding mode where the porphyrin is intercalated to the DNA. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.11841447
title: Understanding structure-based dynamic interactions of antihypertensive peptides extracted from food sources

description: Functional foods are emerging as essential healthy nutritional component due to their abundant wellbeing benefits. Especially the food-derived peptides are considered as key components for playing their biologically active roles. One such robust therapeutics that already exploited with food peptides that help treating high blood pressure via targeting Angiotensin-Converting Enzyme (ACE). This <i>in silico</i> study demonstrated the inhibitory potential of antihypertensive peptides derived from food sources. This study involves an intensive structure-based analysis of enzyme-peptide interactions using Molecular Dynamics (MD) simulations. Interestingly, this study will help us to get deeper understanding on how food peptides achieve successful inhibition of ACE. In this study, the peptide-enzyme complexes revealed two binding pockets, A and B, on either side of the active site Zn atom. Pocket B has a smaller binding site volume than pocket A, comprised of β-sheets and the active site opening cleft. The interface of the binding sites showed that the enzyme structure was negative to neutral charge, and the peptide structure was positive to neutral charge. The dynamics of complex structures of seven highly potential peptides were performed for 20 ns each at 300 K. Comparative analysis of RMSD, RMSF and binding energies show the enzyme-peptide complexes and the overall stability of apo-enzyme. Importantly, two peptides AFKAWAVAR and IWHHTF showed the highest variation in their RMSD as compared to the apo-enzyme. This study will further be useful for the assessment of the characteristics to predict novel inhibitory peptides that can be generated from food proteins. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.11841447.v1
title: Understanding structure-based dynamic interactions of antihypertensive peptides extracted from food sources

description: Functional foods are emerging as essential healthy nutritional component due to their abundant wellbeing benefits. Especially the food-derived peptides are considered as key components for playing their biologically active roles. One such robust therapeutics that already exploited with food peptides that help treating high blood pressure via targeting Angiotensin-Converting Enzyme (ACE). This <i>in silico</i> study demonstrated the inhibitory potential of antihypertensive peptides derived from food sources. This study involves an intensive structure-based analysis of enzyme-peptide interactions using Molecular Dynamics (MD) simulations. Interestingly, this study will help us to get deeper understanding on how food peptides achieve successful inhibition of ACE. In this study, the peptide-enzyme complexes revealed two binding pockets, A and B, on either side of the active site Zn atom. Pocket B has a smaller binding site volume than pocket A, comprised of β-sheets and the active site opening cleft. The interface of the binding sites showed that the enzyme structure was negative to neutral charge, and the peptide structure was positive to neutral charge. The dynamics of complex structures of seven highly potential peptides were performed for 20 ns each at 300 K. Comparative analysis of RMSD, RMSF and binding energies show the enzyme-peptide complexes and the overall stability of apo-enzyme. Importantly, two peptides AFKAWAVAR and IWHHTF showed the highest variation in their RMSD as compared to the apo-enzyme. This study will further be useful for the assessment of the characteristics to predict novel inhibitory peptides that can be generated from food proteins. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.11864394
title: Effect of periphery cationic substituents of porphyrin on the B-Z transition of poly[d(A-T)<sub>2</sub>], poly[d(G-C)<sub>2</sub>] and their binding modes

description: The binding mode of cationic porphyrin (<i>trans</i>-BMPyP) with poly[d(G-C)<sub>2</sub>] and poly[d(A-T)<sub>2</sub>] was examined according to the site of the periphery cationic methyl pyridine ion of the cationic porphyrin (<i>o-, m-, p-</i>) as well as the possibility of a B-Z transition depending on the binding modes by measuring the absorption spectrum and circular dichroism (CD). The negative band found in the soret region showed the intercalation mode of <i>m-</i> and <i>p-trans-</i>BMPyP-poly[d(G-C)<sub>2</sub>] to the DNA base pairs, but no B-Z transition was induced. On the other hand, the distinctive bisignate band found in the soret region of the CD spectrum for <i>m-</i> and <i>p-trans-</i>BMPyP-poly[d(A-T)<sub>2</sub>] suggests that <i>m-</i> and <i>p-trans-</i>BMPyP have an effective extensive stacking-based binding mode along with the skeleton of poly[d(A-T)<sub>2</sub>], wherein the B-Z transition was induced through extensive stacking. The difference in binding mode was attributed to the difference in the molecular structure depending on the site of the periphery cationic methyl pyridine ion in the cationic porphyrin. In other words, <i>o-trans-</i>BMPyP is nonplanar because of the steric hindrance of the cationic methyl pyridine ion at the <i>o-</i>site. In contrast, <i>m-</i> and <i>p-trans-</i>BMPyP are planar, but not all porphyrins with a planar structure undergo the B-Z transition. In conclusion, a B-Z transition is induced if the structure of a porphyrin is planar and the binding mode allows the porphyrins to be stacked effectively along the DNA skeleton, not in a binding mode where the porphyrin is intercalated to the DNA. Communicated by Ramaswamy H. Sarma
DOI: 10.17188/1689225
title: Materials Data on LiAs(XeF4)3 by Materials Project

description: LiAs(XeF4)3 crystallizes in the monoclinic P2_1 space group. The structure is two-dimensional and consists of two LiAs(XeF4)3 sheets oriented in the (0, 1, 0) direction. there are three inequivalent Xe sites. In the first Xe site, Xe is bonded in a linear geometry to two F atoms. Both Xe–F bond lengths are 2.08 Å. In the second Xe site, Xe is bonded in a linear geometry to two F atoms. Both Xe–F bond lengths are 2.08 Å. In the third Xe site, Xe is bonded in a linear geometry to two F atoms. There are one shorter (2.05 Å) and one longer (2.10 Å) Xe–F bond lengths. Li is bonded to six F atoms to form LiF6 octahedra that share a cornercorner with one AsF6 octahedra. The corner-sharing octahedral tilt angles are 31°. There are a spread of Li–F bond distances ranging from 2.01–2.10 Å. As is bonded to six F atoms to form AsF6 octahedra that share a cornercorner with one LiF6 octahedra. The corner-sharing octahedral tilt angles are 31°. There are a spread of As–F bond distances ranging from 1.77–1.82 Å. There are twelve inequivalent F sites. In the first F site, F is bonded in a single-bond geometry to one As atom. In the second F site, F is bonded in a bent 120 degrees geometry to one Xe and one Li atom. In the third F site, F is bonded in a bent 120 degrees geometry to one Xe and one Li atom. In the fourth F site, F is bonded in a bent 120 degrees geometry to one Xe and one Li atom. In the fifth F site, F is bonded in a bent 120 degrees geometry to one Xe and one Li atom. In the sixth F site, F is bonded in a bent 120 degrees geometry to one Xe and one Li atom. In the seventh F site, F is bonded in a single-bond geometry to one Xe atom. In the eighth F site, F is bonded in a bent 150 degrees geometry to one Li and one As atom. In the ninth F site, F is bonded in a single-bond geometry to one As atom. In the tenth F site, F is bonded in a single-bond geometry to one As atom. In the eleventh F site, F is bonded in a single-bond geometry to one As atom. In the twelfth F site, F is bonded in a single-bond geometry to one As atom.
DOI: 10.6084/m9.figshare.11506812.v2
title: Synthesis, characterization and anti-inflammatory activity evaluation of 1,2,4-triazole and its derivatives as a potential scaffold for the synthesis of drugs against prostaglandin-endoperoxide synthase

description: Substituted 1,2,4-triazole nucleus is common in several drugs used in a variety of clinical conditions including infections, hypoglycemia, hypertension and cancer. In this study, we synthesized 1,2,4-triazole and its 16 hydrazone derivatives (B1–B16), characterized them by IR, NMR and Mass spectroscopy, and evaluated their radical scavenging and anti-inflammatory activities <i>in vitro</i> and <i>in vivo</i>. Out of 16 derivatives, five (B1, B5, B6, B9, and B13) demonstrated a significant radical scavenging and anti-inflammatory activity <i>in vitro</i>. B6, which possessed two electron-donating hydroxyl groups, was most active among all. Molecular docking and MD simulation of the complex of B6 with prostaglandin-endoperoxide synthase (PTGS) or cyclooxygenase (COX) showed that B6 occupied celecoxib binding site in COX with high affinity (the binding free energy of the complex with COX-1 was –10.5, and –11.2 kcal/mol with COX-2). Maximum anti-inflammatory activity was also shown by the B6 derivative <i>in vivo,</i> in the rat model of carrageenan-induced inflammation. B6, along with four other derivatives (B1, B5, B9 and B13) exhibited 80–90% free radical scavenging activity. The IC<sub>50</sub> values of these compounds were ≥40 µM. Griess nitrite and dichloro-dihydro-fluorescein-diacetate assays suggested a significant inhibition of nitric oxide and reactive oxygen species, especially by B6 and B9. Taken together, out of 16 derivatives, B6 is reported to have highest anti-inflammatory and antioxidant activity at a low dose level, which may be attributed to its two electron-donating hydroxyls. B6 is proposed to be an important scaffold for the synthesis of new drugs against PTGS for use in a myriad of inflammatory and infectious diseases. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.11522451
title: From normal to competo-allosteric regulation: insights into the binding pattern dynamics of DSPI protein of <i>Pseudomonas aeruginosa</i>

description: DSPI, a putative enoyl-coenzyme A (CoA) hydratase/isomerase, is anticipated to be involved in the synthesis of cis-2-decenoic acid (CDA), a quorum sensing (QS) signal molecule present in the superbug <i>Pseudomonas aeruginosa</i>. The current study not only adapts a broad-spectrum strategy for the lucid design of small molecule modulators but also provides novel allosteric inhibitors for DSPI, to investigate its function and potential as a therapeutic target. Docking analysis revealed that the compound 10252273, bound to the specific allosteric site, interacted with Glu118, unique amino acid residue of the active binding pocket, hence indicates the presence of a competitive allosteric site. The current study thus identifies and characterizes inhibitors by targeting the normal binding site and also reports the presence of the competo-allosteric site in the same binding tunnel as the normal site. Molecular docking studies proposed two chemical compounds that share a benzamide-benzimidazole (BB) backbone as potent inhibitors that can obstruct the mechanism of DSPI by targeting both the normal and proposed allosteric binding sites. MD simulations further revealed the disruption of the normal binding site due to the displacement of critical residues Cys146 and Glu118. The rearrangement of H-bond pattern, pi-pi interactions, and strong hydrophobic interactions were observed at both the binding sites. The allosteric pocket inhibitor exhibited improved binding energy than the normal site inhibitor based on MMGBSA and MMPBSA analysis. With subsequent characterization, the current study reveals the allosteric binding site and provides insights into the drug binding mechanism of DSPI. Communicated by Ramaswamy H. Sarma
DOI: 10.17188/1689226
title: Materials Data on Eu2AlP3Pt7 by Materials Project

description: Eu2Pt7AlP3 crystallizes in the tetragonal I-4m2 space group. The structure is three-dimensional. Eu2+ is bonded in a 9-coordinate geometry to nine Pt2- atoms. There are a spread of Eu–Pt bond distances ranging from 3.10–3.47 Å. There are four inequivalent Pt2- sites. In the first Pt2- site, Pt2- is bonded in a 12-coordinate geometry to two equivalent Eu2+, six Pt2-, two equivalent Al3+, and two equivalent P+2.33+ atoms. There are two shorter (2.82 Å) and four longer (2.89 Å) Pt–Pt bond lengths. Both Pt–Al bond lengths are 2.82 Å. Both Pt–P bond lengths are 2.43 Å. In the second Pt2- site, Pt2- is bonded in a 12-coordinate geometry to two equivalent Eu2+, six Pt2-, two equivalent Al3+, and two equivalent P+2.33+ atoms. Both Pt–Pt bond lengths are 2.79 Å. Both Pt–Al bond lengths are 2.79 Å. Both Pt–P bond lengths are 2.45 Å. In the third Pt2- site, Pt2- is bonded in a 3-coordinate geometry to five equivalent Eu2+ and three P+2.33+ atoms. There are two shorter (2.35 Å) and one longer (2.37 Å) Pt–P bond lengths. In the fourth Pt2- site, Pt2- is bonded to eight Pt2- and four equivalent Al3+ atoms to form distorted PtAl4Pt8 cuboctahedra that share corners with four equivalent PtAl4Pt8 cuboctahedra, faces with four equivalent PtAl4Pt8 cuboctahedra, and faces with four equivalent AlPt12 cuboctahedra. All Pt–Al bond lengths are 2.89 Å. Al3+ is bonded to twelve Pt2- atoms to form AlPt12 cuboctahedra that share corners with four equivalent AlPt12 cuboctahedra, faces with four equivalent PtAl4Pt8 cuboctahedra, and faces with four equivalent AlPt12 cuboctahedra. There are two inequivalent P+2.33+ sites. In the first P+2.33+ site, P+2.33+ is bonded in a 5-coordinate geometry to five Pt2- atoms. In the second P+2.33+ site, P+2.33+ is bonded to four equivalent Pt2- atoms to form corner-sharing PPt4 tetrahedra.
DOI: 10.6084/m9.figshare.11522451.v2
title: From normal to competo-allosteric regulation: insights into the binding pattern dynamics of DSPI protein of <i>Pseudomonas aeruginosa</i>

description: DSPI, a putative enoyl-coenzyme A (CoA) hydratase/isomerase, is anticipated to be involved in the synthesis of cis-2-decenoic acid (CDA), a quorum sensing (QS) signal molecule present in the superbug <i>Pseudomonas aeruginosa</i>. The current study not only adapts a broad-spectrum strategy for the lucid design of small molecule modulators but also provides novel allosteric inhibitors for DSPI, to investigate its function and potential as a therapeutic target. Docking analysis revealed that the compound 10252273, bound to the specific allosteric site, interacted with Glu118, unique amino acid residue of the active binding pocket, hence indicates the presence of a competitive allosteric site. The current study thus identifies and characterizes inhibitors by targeting the normal binding site and also reports the presence of the competo-allosteric site in the same binding tunnel as the normal site. Molecular docking studies proposed two chemical compounds that share a benzamide-benzimidazole (BB) backbone as potent inhibitors that can obstruct the mechanism of DSPI by targeting both the normal and proposed allosteric binding sites. MD simulations further revealed the disruption of the normal binding site due to the displacement of critical residues Cys146 and Glu118. The rearrangement of H-bond pattern, pi-pi interactions, and strong hydrophobic interactions were observed at both the binding sites. The allosteric pocket inhibitor exhibited improved binding energy than the normal site inhibitor based on MMGBSA and MMPBSA analysis. With subsequent characterization, the current study reveals the allosteric binding site and provides insights into the drug binding mechanism of DSPI. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.11506812
title: Synthesis, characterization and anti-inflammatory activity evaluation of 1,2,4-triazole and its derivatives as a potential scaffold for the synthesis of drugs against prostaglandin-endoperoxide synthase

description: Substituted 1,2,4-triazole nucleus is common in several drugs used in a variety of clinical conditions including infections, hypoglycemia, hypertension and cancer. In this study, we synthesized 1,2,4-triazole and its 16 hydrazone derivatives (B1–B16), characterized them by IR, NMR and Mass spectroscopy, and evaluated their radical scavenging and anti-inflammatory activities <i>in vitro</i> and <i>in vivo</i>. Out of 16 derivatives, five (B1, B5, B6, B9, and B13) demonstrated a significant radical scavenging and anti-inflammatory activity <i>in vitro</i>. B6, which possessed two electron-donating hydroxyl groups, was most active among all. Molecular docking and MD simulation of the complex of B6 with prostaglandin-endoperoxide synthase (PTGS) or cyclooxygenase (COX) showed that B6 occupied celecoxib binding site in COX with high affinity (the binding free energy of the complex with COX-1 was –10.5, and –11.2 kcal/mol with COX-2). Maximum anti-inflammatory activity was also shown by the B6 derivative <i>in vivo,</i> in the rat model of carrageenan-induced inflammation. B6, along with four other derivatives (B1, B5, B9 and B13) exhibited 80–90% free radical scavenging activity. The IC<sub>50</sub> values of these compounds were ≥40 µM. Griess nitrite and dichloro-dihydro-fluorescein-diacetate assays suggested a significant inhibition of nitric oxide and reactive oxygen species, especially by B6 and B9. Taken together, out of 16 derivatives, B6 is reported to have highest anti-inflammatory and antioxidant activity at a low dose level, which may be attributed to its two electron-donating hydroxyls. B6 is proposed to be an important scaffold for the synthesis of new drugs against PTGS for use in a myriad of inflammatory and infectious diseases. Communicated by Ramaswamy H. Sarma
DOI: 10.17188/1689227
title: Materials Data on Li(Mo4O5)2 by Materials Project

description: Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations
DOI: 10.6084/m9.figshare.11532999.v2
title: Structure-based virtual screening, free energy of binding and molecular dynamics simulations to propose novel inhibitors of Mtb-MurB oxidoreductase enzyme

description: Currently, the growing incidence of drug resistance toward tuberculosis intensified the need for discovery of novel targets and their inhibitors. The enzyme MurB which is involved in one of the steps for peptidoglycan biosynthesis is an effective target that can produce drugs having lesser side-effects. Recently the only crystal structure of Mycobacterium Tuberculosis MurB has been deposited and, therefore, in the present study, we have used this as a target for virtual screening of drug-like molecules from the ZINC Database. We have also designed a complete workflow for the process which resulted in 12 hit compounds that have good docking scores, Δ<i>G<sub>bind</sub></i>, and Glide energy. The hits obtained have also been found to share structural features with some known antibiotics such as Amoxicillin. Furthermore, MD simulations on the top most hit L1 displayed its stable binding with the enzyme. Thus, this study has proved helpful in proposing novel inhibitors for MurB enzyme that can be tested against various TB strains. Communicated by Ramaswamy H. Sarma