• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.111-116
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• 2014

Objective: To study potential targets of Danshensu via dual inverse docking. Method: PharmMapper and idTarget servers were used as tools, and the results were checked with the molecular docking program autodock vina in PyRx 0.8. Result: The disease-related target HRas was rated top, with a pharmacophore model matching well the molecular features of Danshensu. In addition, docking results indicated that the complex was also matched in terms of structure, H-bonds, and hydrophobicity. Conclusion: Dual inverse docking indicates that HRas may be a potential anticancer target of Danshensu. This approach can provide useful information for studying pharmacological effects of agents of interest.

• CELLMED
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• v.3 no.2
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• pp.12.1-12.4
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• 2013

Identification of target protein is an important procedure in the course of drug discovery. Because of complexity, action mechanisms of herbal medicine are rather obscure, unlike small-molecular drugs. Inverse docking simulation is a reverse use of molecular docking involving multiple target searches for known chemical structure. This methodology can be applied in the field of target fishing and toxicity prediction for herbal compounds as well as known drug molecules. The aim of this review is to introduce a series of in silico works for predicting potential drug targets and side-effects based on inverse docking simulations.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4301-4305
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• 2014

Tanshinone IIA is a pharmacologically active ingredient extracted from Danshen, a Chinese traditional medicine. Its molecular mechanisms are still unclear. The present study utilized computational approaches to uncover the potential targets of this compound. In this research, PharmMapper server was used as the inverse docking tool andnd the results were verified by Autodock vina in PyRx 0.8, and by DRAR-CPI, a server for drug repositioning via the chemical-protein interactome. Results showed that the retinoic acid receptor alpha ($RAR{\alpha}$), a target protein in acute promyelocytic leukemia (APL), was in the top rank, with a pharmacophore model matching well the molecular features of Tanshinone IIA. Moreover, molecular docking and drug repurposing results showed that the complex was also matched in terms of structure and chemical-protein interactions. These results indicated that $RAR{\alpha}$ may be a potential target of Tanshinone IIA for APL. The study can provide useful information for further biological and biochemical research on natural compounds.

• Genomics & Informatics
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• v.19 no.1
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• pp.9.1-9.5
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• 2021

Mammalian olfactory receptors are a family of G protein-coupled receptors (GPCRs) that occupy a large part of the genome. In human genes, olfactory receptors account for more than 40% of all GPCRs. Several types of GPCR structures have been identified, but there is no single olfactory receptor whose structure has been determined experimentally to date. The aim of this study was to model the interactions between an olfactory receptor and its ligands at the molecular level to provide hints on the binding modes between the OR2W1 olfactory receptor and its agonists and inverse agonists. The results demonstrated the modes of ligand binding in a three-dimensional model of OR2W1 and showed a statistically significant difference in binding affinity to the olfactory receptor between agonists and inverse agonists.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5605-5611
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• 2012

Background: In the last two decades, pioneering research on anti-tumour activity of saffron has shed light on the role of crocetin, picrocrocin and safranal, as broad spectrum anti-neoplastic agents. However, the exact mechanisms have yet to be elucidated. Identification and characterization of the targets of bioactive constituents will play an imperative role in demystifying the complex anti-neoplastic machinery. Methods: In the quest of potential target identification, a dual virtual screening approach utilizing two inverse screening systems, one predicated on idTarget and the other on PharmMapper was here employed. A set of target proteins associated with multiple forms of cancer and ranked by Fit Score and Binding energy were obtained from the two independent inverse screening platforms. The validity of the results was checked by meticulously analyzing the post-docking binding pose of the picrocrocin with Hsp90 alpha in AutoDock. Results: The docking pose reveals that electrostatic and hydrogen bonds play the key role in inter-molecular interactions in ligand binding. Picrocrocin binds to the Hsp90 alpha with a definite orientation appropriate for nucleophilic attacks by several electrical residues inside the Hsp90-alpha ATPase catalytic site. Conclusion: This study reveals functional information about the anti-tumor mechanism of saffron bioactive constituents. Also, a tractable set of anti-neoplastic targets for saffron has been generated in this study which can be further authenticated by in vivo and in vitro experiments.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3735-3742
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• 2013

Background: Cardamom (Elettaria cardamom), also known as "Queen of Spices", has been traditionally used as a culinary ingredient due to its pleasant aroma and taste. In addition to this role, studies on cardamom have demonstrated cancer chemopreventive potential in in vitro and in vivo systems. Nevertheless, the precise poly-pharmacological nature of naturally occurring chemo-preventive compounds in cardamom has still not been fully demystified. Methods:In this study, an effort has been made to identify the proapoptopic, anti-inflammatory, anti-proliferative, anti-invasive and anti-angiogenic targets of Cardamom's bioactive principles (eucalyptol, alpha-pinene, beta-pinene, d-limonene and geraniol) by employing a dual reverse virtual screening protocol. Experimentally proven target information of the bioactive principles was annotated from bioassay databases and compared with the virtually screened set of targets to evaluate the reliability of the computational identification. To study the molecular interaction pattern of the anti-tumor action, molecular docking simulation was performed with Auto Dock Pyrx. Interaction studies of binding pose of eucalyptol with Caspase 3 were conducted to obtain an insight into the interacting amino acids and their inter-molecular bondings. Results:A prioritized list of target proteins associated with multiple forms of cancer and ranked by their Fit Score (Pharm Mapper) and descending 3D score (Reverse Screen 3D) were obtained from the two independent inverse screening platforms. Molecular docking studies exploring the bioactive principle targeted action revealed that H- bonds and electrostatic interactions forms the chief contributing factor in inter-molecular interactions associated with anti-tumor activity. Eucalyptol binds to the Caspase 3 with a specific framework that is well-suited for nucleophilic attacks by polar residues inside the Caspase 3 catalytic site. Conclusion:This study revealed vital information about the poly-pharmacological anti-tumor mode-of-action of essential oils in cardamom. In addition, a probabilistic set of anti-tumor targets for cardamom was generated, which can be further confirmed by in vivo and in vitro experiments.

• Bulletin of the Korean Chemical Society
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• v.31 no.1
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• pp.52-58
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• 2010

Human histamine H1 receptor (HHR1) is a G protein-coupled receptor and a primary target for antiallergic therapy. Here, the ligand-based three-dimensional pharmacophore models were built from a set of known HHR1 inverse agonists using HypoGen module of CATALYST software. All ten generated pharmacophore models consist of five essential features: hydrogen bond acceptor, ring aromatic, positive ionizable and two hydrophobic functions. Best model had a correlation coefficient of 0.854 for training set compounds and it was validated with an external test set with a high correlation value of 0.925. Using this model Maybridge database containing 60,000 compounds was screened for potential leads. A rigorous screening for drug-like compounds unveiled RH01692 and SPB00834, two novel molecules for HHR1 with good CATALYST fit and estimated activity values. The new lead molecules were docked into the active site of constructed HHR1 homology model based on recently crystallized squid rhodopsin as template. Both the hit compounds were found to have critical interactions with Glu177, Phe432 and other important amino acids. The interpretations of this study may effectively be deployed in designing of novel HHR1 inverse agonists.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.22 no.4
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• pp.483-492
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• 2021

Agastachis Herba (AH) to treat anorexia and nausea and its antidiabetic efficacy was recently reported. This study examined the antioxidant activities and chemical constituents of AH and predicted the target proteins of each compound using in silico approaches. The results showed that EC50 values of AH methanol extract for DPPH and ABTS radical scavenging were 78.6 ㎍/mL and 31.0 ㎍/mL, respectively. Compared to the EC50 values of ascorbic acid (9.9 ㎍/mL, 5.2 ㎍/mL), the AH methanol extract possessed excellent antioxidant activities. Rosmarinic acid, tilianin, agastachoside, and acetin were confirmed as the major compounds of extracts by qualitative analysis performed with HPLC-PDA-MS/MS. The antidiabetic target proteins of these compounds were predicted by applying a structural similarity and inverse docking methodology using a DIA-DB server. The resulting target proteins were PPAR-γ, DPP IV, glucokinase, α-glucosidase, SGLT2, aldose reductase, and corticosteroid 11-beta-dehydrogenase, some of which have already been proven experimentally as target proteins. Therefore, the in silico methods can be considered valid. Finally, AH were extracted with various solvents to determine the optimal conditions for the extraction of active components. Methanol among organic solvents and 80% ethanol in ethanol-water mixtures were identified as the most effective solvent for the extraction.