cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.22518007
title: Virtual screening, molecular docking, molecular dynamics and quantum chemical studies on (2-methoxy-4-prop-2-enylphenyl) <i>N</i>-(2-methoxy-4-nitrophenyl) carbamate: a novel inhibitor of hepatocellular carcinoma

description: HDAC protein is associated with hepatocellular carcinoma. Different medicinal plants were selected for this study to analyze the inhibitory efficacy against the target protein, HDAC. Using virtual screening, we filtered out the best compounds, and molecular docking (XP) was carried out for the top compounds which filtered out. The molecular docking results showed that the title compound (2-methoxy-4-prop-2-enylphenyl) N-(2-methoxy-4-nitrophenyl) carbamate (MEMNC) has the highest docking score of about −7.7 kcal/mol against the targeted protein histone deacetylase (HDAC) compared with the other selected phytocompounds. From the molecular dynamics analysis, the RMSD and RMSF plots depicted the overall stability of the protein–ligand complex. Toxicity properties show the acceptable range of various kinds of toxicity that were predicted using the ProTox-II server. In addition, DFT quantum chemical and physicochemical properties of the MEMNC molecule were reported. Initially, the molecular structure of the MEMNC molecule was optimized and harmonic vibrational frequencies were calculated using DFT/B3LYP method with a cc-pVTZ basis set using Gaussian 09 program. The calculated vibrational wavenumber values were assigned based on Potential Energy Distribution calculations using the VEDA 4.0 program and correlated well with the previous literature values. The molecule has bioactivity as a result of intramolecular charge transfer interactions, as demonstrated by frontier molecular orbital analysis. Molecular electrostatic potential surface and Mulliken atomic charge distribution analyses validate the reactive sites of the molecule. Thus, the title compound can be used as a potential inhibitor of HDAC protein, which paves the way for designing novel drugs to treat Hepatocellular carcinoma. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.22518007.v1
title: Virtual screening, molecular docking, molecular dynamics and quantum chemical studies on (2-methoxy-4-prop-2-enylphenyl) <i>N</i>-(2-methoxy-4-nitrophenyl) carbamate: a novel inhibitor of hepatocellular carcinoma

description: HDAC protein is associated with hepatocellular carcinoma. Different medicinal plants were selected for this study to analyze the inhibitory efficacy against the target protein, HDAC. Using virtual screening, we filtered out the best compounds, and molecular docking (XP) was carried out for the top compounds which filtered out. The molecular docking results showed that the title compound (2-methoxy-4-prop-2-enylphenyl) N-(2-methoxy-4-nitrophenyl) carbamate (MEMNC) has the highest docking score of about −7.7 kcal/mol against the targeted protein histone deacetylase (HDAC) compared with the other selected phytocompounds. From the molecular dynamics analysis, the RMSD and RMSF plots depicted the overall stability of the protein–ligand complex. Toxicity properties show the acceptable range of various kinds of toxicity that were predicted using the ProTox-II server. In addition, DFT quantum chemical and physicochemical properties of the MEMNC molecule were reported. Initially, the molecular structure of the MEMNC molecule was optimized and harmonic vibrational frequencies were calculated using DFT/B3LYP method with a cc-pVTZ basis set using Gaussian 09 program. The calculated vibrational wavenumber values were assigned based on Potential Energy Distribution calculations using the VEDA 4.0 program and correlated well with the previous literature values. The molecule has bioactivity as a result of intramolecular charge transfer interactions, as demonstrated by frontier molecular orbital analysis. Molecular electrostatic potential surface and Mulliken atomic charge distribution analyses validate the reactive sites of the molecule. Thus, the title compound can be used as a potential inhibitor of HDAC protein, which paves the way for designing novel drugs to treat Hepatocellular carcinoma. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.22083953.v1
title: Design of multi-epitope based vaccine against <i>Mycobacterium tuberculosis:</i> a subtractive proteomics and reverse vaccinology based immunoinformatics approach

description: Tuberculosis is an airborne transmissible disease caused by <i>Mycobacterium tuberculosis</i> that infects millions of lives worldwide. There is still no single comprehensive therapy or preventative available for the lethal illness. Currently, the available vaccine, BCG is ineffectual in preventing the prophylactic adult pulmonary TB and reactivation of latent tuberculosis. Therefore, this investigation was intended to design a new multi-epitope vaccine that can address the existing problems. The subtractive proteomics approach was implemented to prioritize essential, virulence, druggable, and antigenic proteins as suitable vaccine candidates. Furthermore, a reverse vaccinology-based immunoinformatics technique was employed to identify potential B-cell, helper T lymphocytes (HTL), and cytotoxic T lymphocytes (CTL) epitopes from the target proteins. Immune-stimulating adjuvant, linkers, and PADRE (Pan HLA-DR epitopes) amino acid sequences along with the selected epitopes were used to construct a chimeric multi-epitope vaccine. The molecular docking and normal mode analysis (NMA) were carried out to evaluate the binding mode of the designed vaccine with different immunogenic receptors (MHC-I, MHC-II, and Tlr4). In addition, the MD simulation, followed by essential dynamics study and MMPBSA analysis, was carried out to understand the dynamics and stability of the complexes. <i>In-silico</i> cloning was accomplished using <i>E.coli</i> as an expression system to express the designed vaccine successfully. Finally, the immune simulation study has foreseen that our designed vaccine could induce a significant immune response by elevation of different immunoglobulins in the host. However, there is an imperative need for the experimental validation of the designed vaccine in animal models to confer effectiveness and safety. Multi-epitope based vaccine was designed against <i>Mycobacterium tuberculosis</i> using subtractive proteomics and Immunoinformatics approach. The vaccine was found to be antigenic, non-allergenic, immunogenic, and stable based on <i>in-silico</i> prediction. Population coverage analysis of the proposed vaccine predicts an effective response in the world population. The molecular docking, MD simulation, and MM-PBSA study confirm the stable interaction of the vaccine with immunogenic receptors. <i>In silico</i> cloning and immune simulation of the vaccine demonstrated its successful expression in <i>E.coli</i> and induction of immune response in the host. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.22232798.v1
title: In silico screening of inhibitors against human dihydrofolate reductase to identify potential anticancer compounds

description: In all species, dihydrofolate reductase (DHFR) is an essential enzyme that regulates the cellular amount of tetrahydrofolate. Human DHFR (hDHFR) activity inhibition results in tetrahydrofolate depletion and cell death. This property has made hDHFR a therapeutic target for cancer. Methotrexate is a well-known hDHFR inhibitor, but its administration has shown some light to severe adverse effects. Therefore, we aimed to find new potential hDHFR inhibitors using structure-based virtual screening, ADMET prediction, molecular docking, and molecular dynamics simulations. Here, we used the PubChem database to find all compounds with at least 90% structural similarity to known natural DHFR inhibitors. To explore their interaction pattern and estimate their binding affinities, the screened compounds (2023) were subjected to structure-based molecular docking against hDHFR. The fifteen compounds that showed higher binding affinity to the hDHFR than the reference compound (methotrexate) displayed important molecular orientation and interactions with key residues in the enzyme’s active site. These compounds were subjected to Lipinski and ADMET prediction. PubChem CIDs: 46886812 and 638190 were identified as putative inhibitors. In addition, molecular dynamics simulations revealed that the binding of compounds (CIDs: 46886812 and 63819) stabilized the hDHFR structure and caused minor conformational changes. Our findings suggest that two compounds (CIDs: 46886812 and 63819) could be promising potential inhibitors of hDHFR in cancer therapy. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.22083953
title: Design of multi-epitope based vaccine against <i>Mycobacterium tuberculosis:</i> a subtractive proteomics and reverse vaccinology based immunoinformatics approach

description: Tuberculosis is an airborne transmissible disease caused by <i>Mycobacterium tuberculosis</i> that infects millions of lives worldwide. There is still no single comprehensive therapy or preventative available for the lethal illness. Currently, the available vaccine, BCG is ineffectual in preventing the prophylactic adult pulmonary TB and reactivation of latent tuberculosis. Therefore, this investigation was intended to design a new multi-epitope vaccine that can address the existing problems. The subtractive proteomics approach was implemented to prioritize essential, virulence, druggable, and antigenic proteins as suitable vaccine candidates. Furthermore, a reverse vaccinology-based immunoinformatics technique was employed to identify potential B-cell, helper T lymphocytes (HTL), and cytotoxic T lymphocytes (CTL) epitopes from the target proteins. Immune-stimulating adjuvant, linkers, and PADRE (Pan HLA-DR epitopes) amino acid sequences along with the selected epitopes were used to construct a chimeric multi-epitope vaccine. The molecular docking and normal mode analysis (NMA) were carried out to evaluate the binding mode of the designed vaccine with different immunogenic receptors (MHC-I, MHC-II, and Tlr4). In addition, the MD simulation, followed by essential dynamics study and MMPBSA analysis, was carried out to understand the dynamics and stability of the complexes. <i>In-silico</i> cloning was accomplished using <i>E.coli</i> as an expression system to express the designed vaccine successfully. Finally, the immune simulation study has foreseen that our designed vaccine could induce a significant immune response by elevation of different immunoglobulins in the host. However, there is an imperative need for the experimental validation of the designed vaccine in animal models to confer effectiveness and safety. Multi-epitope based vaccine was designed against <i>Mycobacterium tuberculosis</i> using subtractive proteomics and Immunoinformatics approach. The vaccine was found to be antigenic, non-allergenic, immunogenic, and stable based on <i>in-silico</i> prediction. Population coverage analysis of the proposed vaccine predicts an effective response in the world population. The molecular docking, MD simulation, and MM-PBSA study confirm the stable interaction of the vaccine with immunogenic receptors. <i>In silico</i> cloning and immune simulation of the vaccine demonstrated its successful expression in <i>E.coli</i> and induction of immune response in the host. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.22238985
title: Structural modeling and analyses of genetic variations in the human XPC nucleotide excision repair protein

description: Xeroderma pigmentosum C (XPC) is a key initiator in the global genome nucleotide excision repair pathway in mammalian cells. Inherited mutations in the XPC gene can cause xeroderma pigmentosum (XP) cancer predisposition syndrome that dramatically increases the susceptibility to sunlight-induced cancers. Various genetic variants and mutations of the protein have been reported in cancer databases and literature. The current lack of a high-resolution 3-D structure of human XPC makes it difficult to assess the structural impact of the mutations/genetic variations. Using the available high-resolution crystal structure of its yeast ortholog, Rad4, we built a homology model of human XPC protein and compared it with a model generated by AlphaFold. The two models are largely consistent with each other in the structured domains. We have also assessed the degree of conservation for each residue using 966 sequences of XPC orthologs. Our structure- and sequence conservation-based assessments largely agree with the variant’s impact on the protein’s structural stability, computed by FoldX and SDM. Known XP missense mutations such as Y585C, W690S, and C771Y are consistently predicted to destabilize the protein’s structure. Our analyses also reveal several highly conserved hydrophobic regions that are surface-exposed, which may indicate novel intermolecular interfaces that are yet to be characterized. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.22316612
title: Evaluation of SNPs from human IGFBP6 associated with gene expression: an <i>in-silico</i> study

description: In the bloodstream and in local tissues, most IGF molecules are associated with the one of the members of the IGF-binding protein (IGFBP) family, which are divided into six distinct types. IGF-binding proteins have been demonstrated to either decrease or increase the growth-promoting effects of IGFs on cell culture, by extending their half-life. They alter how IGFs interact with the receptors on their cell surfaces. <i>IGFBP6</i> gene is associated with disease <i>in-situ</i> carcinoma. Upregulation or downregulation of <i>IGFBP6</i> gene has been implicated in different types of cancer in humans. Nonsynonymous SNPs changes have the potential to affect the protein’s structure and function. Potential functional SNPs can be assessed before undertaking studies in larger populations because validation of these functional SNPs can be a crucial problem. So, in this <i>in-silico</i> investigation, we used a variety of sequence- and structure-based bioinformatics methods to separate the potential nsSNPs of the <i>IGFBP6</i> gene from the neutral ones. In total of 216 nsSNPs, 5 were found to have potential effects using 5 prediction tools. From which, 2 nsSNPs (R128G and R164H) were selected as potentially damaging due to their presence in highly conserved region and ability to decrease protein stability. Among these 2 nsSNPs, only R164H was found to be associated with Uterine corpus endometrial carcinoma. It was also found that both, upregulation or downregulation of <i>IGFBP6</i> gene can lead to the different types of cancers. The findings of the present study will certainly be valuable in the future large population-based investigations as well as drug discovery, especially developing personalized medicine. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.22238985.v1
title: Structural modeling and analyses of genetic variations in the human XPC nucleotide excision repair protein

description: Xeroderma pigmentosum C (XPC) is a key initiator in the global genome nucleotide excision repair pathway in mammalian cells. Inherited mutations in the XPC gene can cause xeroderma pigmentosum (XP) cancer predisposition syndrome that dramatically increases the susceptibility to sunlight-induced cancers. Various genetic variants and mutations of the protein have been reported in cancer databases and literature. The current lack of a high-resolution 3-D structure of human XPC makes it difficult to assess the structural impact of the mutations/genetic variations. Using the available high-resolution crystal structure of its yeast ortholog, Rad4, we built a homology model of human XPC protein and compared it with a model generated by AlphaFold. The two models are largely consistent with each other in the structured domains. We have also assessed the degree of conservation for each residue using 966 sequences of XPC orthologs. Our structure- and sequence conservation-based assessments largely agree with the variant’s impact on the protein’s structural stability, computed by FoldX and SDM. Known XP missense mutations such as Y585C, W690S, and C771Y are consistently predicted to destabilize the protein’s structure. Our analyses also reveal several highly conserved hydrophobic regions that are surface-exposed, which may indicate novel intermolecular interfaces that are yet to be characterized. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.22316612.v1
title: Evaluation of SNPs from human IGFBP6 associated with gene expression: an <i>in-silico</i> study

description: In the bloodstream and in local tissues, most IGF molecules are associated with the one of the members of the IGF-binding protein (IGFBP) family, which are divided into six distinct types. IGF-binding proteins have been demonstrated to either decrease or increase the growth-promoting effects of IGFs on cell culture, by extending their half-life. They alter how IGFs interact with the receptors on their cell surfaces. <i>IGFBP6</i> gene is associated with disease <i>in-situ</i> carcinoma. Upregulation or downregulation of <i>IGFBP6</i> gene has been implicated in different types of cancer in humans. Nonsynonymous SNPs changes have the potential to affect the protein’s structure and function. Potential functional SNPs can be assessed before undertaking studies in larger populations because validation of these functional SNPs can be a crucial problem. So, in this <i>in-silico</i> investigation, we used a variety of sequence- and structure-based bioinformatics methods to separate the potential nsSNPs of the <i>IGFBP6</i> gene from the neutral ones. In total of 216 nsSNPs, 5 were found to have potential effects using 5 prediction tools. From which, 2 nsSNPs (R128G and R164H) were selected as potentially damaging due to their presence in highly conserved region and ability to decrease protein stability. Among these 2 nsSNPs, only R164H was found to be associated with Uterine corpus endometrial carcinoma. It was also found that both, upregulation or downregulation of <i>IGFBP6</i> gene can lead to the different types of cancers. The findings of the present study will certainly be valuable in the future large population-based investigations as well as drug discovery, especially developing personalized medicine. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.22179206
title: Investigation of novel ligand targeting bromodomain-containing protein 4 (BRD4) for cancer drug discovery: complete pharmacophore approach

description: The Bromodomain (BRD4) and extra-terminal (BET) protein family are reversible; lysine-acetylated epigenetic readers identified as key important epigenetic regulators for protein recognition in posttranslational modifications for targeting cancer for its role in super-enhancers and transcription of oncogene expression in cancer and other forms of cancer and various diseases. Firstly, JQ-1a small potent BET inhibitors, targeting BET proteins were currently in clinical trials to ablate cancer. The identified compounds were taken from the library of preexisting therapeutically potent molecules. The objective of the present study is to identify the potential small molecule inhibitors against BRD4 through <i>in-silico</i> approach for the treatment of cancer. In present study, designed an <i>in-silico</i> screening of small molecules through ligand-based pharmacophore studies against bromodomain-containing protein 4 (BRD-4) protein and used for virtual screening through Database and their binding affinity and interaction of identified molecules were predicted through molecular docking, molecular dynamics simulations for 12 fixed time period, Molecular mechanics (MMGBSA) binding free energy calculations, ADME with drug-likeness properties including violations of lipinski's rule of 5, Jorgensens rule of 3 and other parameters were studied. The docking results indicate from the reported database screened molecules were validated with docking score −7.92 to −4.27Kcal/mol for BRD4-BD1 and the best model identified 21 hits. Among these two drugs were filtered and scrutinized for their ability based on binding modes and common interaction, MMGBSA of the highest affinity −54.53 Kcal/mol of BRD4-BD1 and ADME properties of selected molecules were predicted for its various parameters, dynamics studies evaluating its binding stability using Maestro software. In Conclusion, two BRD4 inhibitors were found to bind strongly in the similar binding sites as JQ-1, highlighting the role of BRD4-BD1. These compounds were identified as promising new options for regulating epigenetics and understanding the structural needs of BRD4 protein, further research in these areas could lead to the development of more effective and targeted cancer drugs. Communicated by Ramaswamy H. Sarma The Bromodomain and extra-C terminal domain (BET) proteins have been identified as an epigenetic approach as a promising targets for cancer. Many small-molecule inhibitors of BRD4 exhibiting a diverse range of acetyl-lysine recognition motifs were collected with different scaffolds biological activities. BRD4 inhibitors provide a novel approach to epigenetic anticancer therapy having significant interest. 3D ligand-based pharmacophore model for BRD4-BD1 and BD2 were generated and screened and further docking and dynamics studies were analyzed. Several new compounds identified as potential BRD4-BD1 inhibitors for various form of tumor’s.
DOI: 10.34740/kaggle/dsv/7175636
title: 2021 World Population (updated daily)