Browse
Submit Data
Databases
API
Help

Dataset Information

11 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Using reverse docking to identify potential targets for ginsenosides.

ABSTRACT: BACKGROUND:Ginsenosides are the main ingredients of ginseng, which, in traditional Eastern medicine, has been claimed to have therapeutic values for many diseases. In order to verify the effects of ginseng that have been empirically observed, we utilized the reverse docking method to screen for target proteins that are linked to specific diseases. METHODS:We constructed a target protein database including 1,078 proteins associated with various kinds of diseases, based on the Potential Drug Target Database, with an added list of kinase proteins. We screened 26 kinds of ginsenosides of this target protein database using docking. RESULTS:We found four potential target proteins for ginsenosides, based on docking scores. Implications of these "hit" targets are discussed. From this screening, we also found four targets linked to possible side effects and toxicities, based on docking scores. CONCLUSION:Our method and results can be helpful for finding new targets and developing new drugs from natural products.

SUBMITTER: Park K

PROVIDER: S-EPMC5628352 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Using reverse docking to identify potential targets for ginsenosides.

Park Kichul K Cho Art E AE

Journal of ginseng research 20161110 4

<h4>Background</h4>Ginsenosides are the main ingredients of ginseng, which, in traditional Eastern medicine, has been claimed to have therapeutic values for many diseases. In order to verify the effects of ginseng that have been empirically observed, we utilized the reverse docking method to screen for target proteins that are linked to specific diseases.<h4>Methods</h4>We constructed a target protein database including 1,078 proteins associated with various kinds of diseases, based on the Poten ...[more]

PMID: 29021701

Similar Datasets

A comparative reverse docking strategy to identify potential antineoplastic targets of tea functional components and binding mode.

Project description:The main functional components of green tea, such as epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG) and epicatechin (EC), are found to have a broad antineoplastic activity. The discovery of their targets plays an important role in revealing the antineoplastic mechanism. Therefore, to identify potential target proteins for tea polyphenols, we have taken a comparative virtual screening approach using two reverse docking systems, one based on Autodock software and the other on Tarfisdock. Two separate in silico workflows were implemented to derive a set of target proteins related to human diseases and ranked by the binding energy score. Several conventional clinically important proteins with anti-tumor effects are screened out from the PDTD protein database as the potential receptors by both procedures. To further analyze the validity of docking results, we study the binding mode of EGCG and the potential target protein Leukotriene A4 hydrolase in detail. We indicate that interactions mediated by electrostatic and hydrogen bond play a key role in ligand binding. EGCG binds to the enzyme with certain orientation and conformation that is suitable for nucleophilic attacks by several electrical residues inside the enzyme's activity cavity. This study provides useful information for studying the antitumor mechanism of tea's functional components. The comparative reverse docking strategy presented generates a tractable set of antineoplastic proteins for future experimental validation as drug targets against tumors.

| S-EPMC3179160 | biostudies-literature

Identification of afzelin potential targets in inhibiting triple-negative breast cancer cell migration using reverse docking.

Project description:Background: Triple-negative breast cancer (TNBC) tends to be aggressive and metastatic, characteristics attributable to its cellular migration capabilities. Afzelin is a chemical compound with anti-metastatic potentials. This study aimed to predict proteins involved in TNBC cell migration which could be inhibited by afzelin.Methods: The protein database was constructed from the Kyoto Encyclopedia of Genes and Genomes pathways collection which related to cell motility, then screened for druggability using SuperTarget and Therapeutic Target Database. The involvement of druggable proteins in the TNBC metastasis process was investigated through existing publications in The National Center for Biotechnology Information PubMed database. Inhibitory potential of afzelin toward target proteins was compared to the proteins' known-inhibitor, using the reverse docking method.Results: Ten proteins identified as potential targets of afzelin, with the top 3 being ERK2, KRas, and FAK, respectively. Afzelin's 3-O-rhamnoside group played a dominant role in forming hydrogen bonds with the target proteins. Further analysis with STRING suggested that afzelin might be able to inhibit chemotaxis and haptotaxis of TNBC cells.Conclusions: Afzelin was predicted to inhibit TNBC cell motility, by targeting ERK2, KRas, and FAK activation.

| S-EPMC7710241 | biostudies-literature

Reverse screening approach to identify potential anti-cancer targets of dipyridamole.

Project description:Dipyridamole (DIP) inhibits thrombus formation when given chronically, and causes vasodilation over a short time. To date, DIP can increase the anticancer drugs (5-fluorouracil, methotrexate, piperidine, vincristine) concentration in cancer cells and hence enhance the efficacy of treatment cancer. The inhibition of DIP may result in increased 5-fluorouracil efficacy and diminish the drug side effects. But the actual molecular targets remain unknown. In this study, reverse protein-ligands docking, and quantum mechanics were used to search for the potential molecular targets of DIP. The quantum mechanics calculation was performed by using Gaussian 03 program package. Reverse pharmacophore mapping was used to search for potential molecular target candidates for a given small molecule. The docking study was used for exploring the potential anti-cancer targets of dipyridamole. The two predicted binders with the statistically significant prediction are dihydropyrimidine dehydrogenase (DPD) (PDB Id: 1GTE) and human spindle checkpoint kinase Bub1 (PDB Id: 3E7E). Structure analysis suggests that electrostatic interaction and hydrogen bonding play an important role in their binding process. The strong functional linkage of DIP and 5FU supports our prediction. In conclusion, these results generate a tractable set of anticancer proteins. The exploration of polypharmacology will provide us new opportunities in treating systematic diseases, such as the cancers. The results would generate a tractable set of anticancer target proteins for future experimental validations.

| S-EPMC5209474 | biostudies-literature

Exploring gene knockout strategies to identify potential drug targets using genome-scale metabolic models.

Project description:Research on new cancer drugs is performed either through gene knockout studies or phenotypic screening of drugs in cancer cell-lines. Both of these approaches are costly and time-consuming. Computational framework, e.g., genome-scale metabolic models (GSMMs), could be a good alternative to find potential drug targets. The present study aims to investigate the applicability of gene knockout strategies to be used as the finding of drug targets using GSMMs. We performed single-gene knockout studies on existing GSMMs of the NCI-60 cell-lines obtained from 9 tissue types. The metabolic genes responsible for the growth of cancerous cells were identified and then ranked based on their cellular growth reduction. The possible growth reduction mechanisms, which matches with the gene knockout results, were described. Gene ranking was used to identify potential drug targets, which reduce the growth rate of cancer cells but not of the normal cells. The gene ranking results were also compared with existing shRNA screening data. The rank-correlation results for most of the cell-lines were not satisfactory for a single-gene knockout, but it played a significant role in deciding the activity of drug against cell proliferation, whereas multiple gene knockout analysis gave better correlation results. We validated our theoretical results experimentally and showed that the drugs mitotane and myxothiazol can inhibit the growth of at least four cell-lines of NCI-60 database.

| S-EPMC7794450 | biostudies-literature

In vivo inducible reverse genetics in patients' tumors to identify individual therapeutic targets.

Project description:High-throughput sequencing describes multiple alterations in individual tumors, but their functional relevance is often unclear. Clinic-close, individualized molecular model systems are required for functional validation and to identify therapeutic targets of high significance for each patient. Here, we establish a Cre-ERT2-loxP (causes recombination, estrogen receptor mutant T2, locus of X-over P1) based inducible RNAi- (ribonucleic acid interference) mediated gene silencing system in patient-derived xenograft (PDX) models of acute leukemias in vivo. Mimicking anti-cancer therapy in patients, gene inhibition is initiated in mice harboring orthotopic tumors. In fluorochrome guided, competitive in vivo trials, silencing of the apoptosis regulator MCL1 (myeloid cell leukemia sequence 1) correlates to pharmacological MCL1 inhibition in patients´ tumors, demonstrating the ability of the method to detect therapeutic vulnerabilities. The technique identifies a major tumor-maintaining potency of the MLL-AF4 (mixed lineage leukemia, ALL1-fused gene from chromosome 4) fusion, restricted to samples carrying the translocation. DUX4 (double homeobox 4) plays an essential role in patients' leukemias carrying the recently described DUX4-IGH (immunoglobulin heavy chain) translocation, while the downstream mediator DDIT4L (DNA-damage-inducible transcript 4 like) is identified as therapeutic vulnerability. By individualizing functional genomics in established tumors in vivo, our technique decisively complements the value chain of precision oncology. Being broadly applicable to tumors of all kinds, it will considerably reinforce personalizing anti-cancer treatment in the future.

| S-EPMC8476619 | biostudies-literature

Identification of gefitinib off-targets using a structure-based systems biology approach; their validation with reverse docking and retrospective data mining.

Project description:Gefitinib, an EGFR tyrosine kinase inhibitor, is used as FDA approved drug in breast cancer and non-small cell lung cancer treatment. However, this drug has certain side effects and complications for which the underlying molecular mechanisms are not well understood. By systems biology based in silico analysis, we identified off-targets of gefitinib that might explain side effects of this drugs. The crystal structure of EGFR-gefitinib complex was used for binding pocket similarity searches on a druggable proteome database (Sc-PDB) by using IsoMIF Finder. The top 128 hits of putative off-targets were validated by reverse docking approach. The results showed that identified off-targets have efficient binding with gefitinib. The identified human specific off-targets were confirmed and further analyzed for their links with biological process and clinical disease pathways using retrospective studies and literature mining, respectively. Noticeably, many of the identified off-targets in this study were reported in previous high-throughput screenings. Interestingly, the present study reveals that gefitinib may have positive effects in reducing brain and bone metastasis, and may be useful in defining novel gefitinib based treatment regime. We propose that a system wide approach could be useful during new drug development and to minimize side effect of the prospective drug.

| S-EPMC5032012 | biostudies-literature

Examination of lipid profiles in abdominal fascial healing using MALDI-TOF to identify potential therapeutic targets.

Project description:BackgroundFailure of fascial healing in the abdominal wall can result in incisional hernia, which is one of the most common complications after laparotomy. Understanding the molecular healing process of abdominal fascia may provide lipid markers of incisional hernia or therapeutic targets that allow prevention or treatment of incisional hernias.PurposeThis study aims to investigate temporal and in situ changes of lipids during the normal healing process of abdominal fascia in the first postoperative week.MethodsOpen hemicolectomy was performed in a total of 35 Wistar rats. The midline fascia was closed identically for all rats using a single continuous suturing technique. These animals were sacrificed with equal numbers (n = 5) at each of 7-time points (6, 12, 24, 48, 72, 120, and 168 h. The local and temporal changes of lipids were examined with mass spectrometry imaging and correlated to histologically scored changes during healing using hematoxylin and eosin staining.ResultsTwo phosphatidylcholine lipid species (PC O-38:5 and PC 38:4) and one phosphatidylethanolamine lipid (PE O-16:1_20:4) were found to significantly correlate with temporal changes of inflammation. A phosphatidylcholine (PC 32:0) and a monosialodihexosylganglioside (GM3 34:1;2) were found to correlate with fibroblast cell growth.ConclusionGlycerophospholipids and gangliosides are strongly involved in the normal healing process of abdominal fascia and their locally fluctuating concentrations are considered as potential lipid markers and therapeutic targets of fascial healing.

| S-EPMC8600998 | biostudies-literature

In-Silico Determination of Insecticidal Potential of Vip3Aa-Cry1Ac Fusion Protein Against Lepidopteran Targets Using Molecular Docking.

Project description:Study and research of Bt (Bacillus thuringiensis) transgenic plants have opened new ways to combat insect pests. Over the decades, however, insect pests, especially the Lepidopteran, have developed tolerance against Bt delta-endotoxins. Such issues can be addressed through the development of novel toxins with greater toxicity and affinity against a broad range of insect receptors. In this computational study, functional domains of Bacillus thuringiensis crystal delta-endotoxin (Cry1Ac) insecticidal protein and vegetative insecticidal protein (Vip3Aa) have been fused to develop a broad-range Vip3Aa-Cry1Ac fusion protein. Cry1Ac and Vip3Aa are non-homologous insecticidal proteins possessing receptors against different targets within the midgut of insects. The insecticidal proteins were fused to broaden the insecticidal activity. Molecular docking analysis of the fusion protein against aminopeptidase-N (APN) and cadherin receptors of five Lepidopteran insects (Agrotis ipsilon, Helicoverpa armigera, Pectinophora gossypiella, Spodoptera exigua, and Spodoptera litura) revealed that the Ser290, Ser293, Leu337, Thr340, and Arg437 residues of the fusion protein are involved in the interaction with insect receptors. The Helicoverpa armigera cadherin receptor, however, showed no interaction, which might be due to either loss or burial of interactive residues inside the fusion protein. These findings revealed that the Vip3Aa-Cry1Ac fusion protein has a strong affinity against Lepidopteran insect receptors and hence has a potential to be an efficient broad-range insecticidal protein.

| S-EPMC4667078 | biostudies-literature

Protein Targets of Frankincense: A Reverse Docking Analysis of Terpenoids from Boswellia Oleo-Gum Resins.

Project description:Background: Frankincense, the oleo-gum resin of Boswellia trees, has been used in traditional medicine since ancient times. Frankincense has been used to treat wounds and skin infections, inflammatory diseases, dementia, and various other conditions. However, in many cases, the biomolecular targets for frankincense components are not well established. Methods: In this work, we have carried out a reverse docking study of Boswellia diterpenoids and triterpenoids with a library of 16034 potential druggable target proteins. Results:Boswellia diterpenoids showed selective docking to acetylcholinesterase, several bacterial target proteins, and HIV-1 reverse transcriptase. Boswellia triterpenoids targeted the cancer-relevant proteins (poly(ADP-ribose) polymerase-1, tankyrase, and folate receptor ?), inflammation-relevant proteins (phospholipase A2, epoxide hydrolase, and fibroblast collagenase), and the diabetes target 11?-hydroxysteroid dehydrogenase. Conclusions: The preferential docking of Boswellia terpenoids is consistent with the traditional uses and the established biological activities of frankincense.

| S-EPMC6163972 | biostudies-literature

Reverse GWAS: Using genetics to identify and model phenotypic subtypes.

Project description:Recent and classical work has revealed biologically and medically significant subtypes in complex diseases and traits. However, relevant subtypes are often unknown, unmeasured, or actively debated, making automated statistical approaches to subtype definition valuable. We propose reverse GWAS (RGWAS) to identify and validate subtypes using genetics and multiple traits: while GWAS seeks the genetic basis of a given trait, RGWAS seeks to define trait subtypes with distinct genetic bases. Unlike existing approaches relying on off-the-shelf clustering methods, RGWAS uses a novel decomposition, MFMR, to model covariates, binary traits, and population structure. We use extensive simulations to show that modelling these features can be crucial for power and calibration. We validate RGWAS in practice by recovering a recently discovered stress subtype in major depression. We then show the utility of RGWAS by identifying three novel subtypes of metabolic traits. We biologically validate these metabolic subtypes with SNP-level tests and a novel polygenic test: the former recover known metabolic GxE SNPs; the latter suggests subtypes may explain substantial missing heritability. Crucially, statins, which are widely prescribed and theorized to increase diabetes risk, have opposing effects on blood glucose across metabolic subtypes, suggesting the subtypes have potential translational value.

| S-EPMC6469799 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data