3D pharmacophore-based virtual screening, docking and density functional theory approach towards the discovery of novel human epidermal growth factor receptor-2 (HER2) inhibitors

Gogoi, Dhrubajyoti; Baruah, Vishwa Jyoti; Chaliha, Amrita Kashyap; Kakoti, Bibhuti Bhusan; Sarma, Diganta; Buragohain, Alak Kumar

doi:10.1016/j.jtbi.2016.09.016

Cited by 21 publications

(9 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Virtual screening based on chemical databases is a fast and accurate approach to identify novel and potential drug (Gogoi et al, 2016 ; Guedes et al, 2016 ). The Hypo1 have used as a 3D query tool to screen the chemical databases like Maybridge (20565), Chembridge (40637), ChemDiv (12620), and Specs (37738).…”

Section: Resultsmentioning

confidence: 99%

Combination of Virtual Screening Protocol by in Silico toward the Discovery of Novel 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors

Sun

et al. 2018

Front. Chem.

View full text Add to dashboard Cite

4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD) is a potent new bleaching herbicide target. Therefore, in silico structure-based virtual screening was performed in order to speed up the identification of promising HPPD inhibitors. In this study, an integrated virtual screening protocol by combining 3D-pharmacophore model, molecular docking and molecular dynamics (MD) simulation was established to find novel HPPD inhibitors from four commercial databases. 3D-pharmacophore Hypo1 model was applied to efficiently narrow potential hits. The hit compounds were subsequently submitted to molecular docking studies, showing four compounds as potent inhibitor with the mechanism of the Fe(II) coordination and interaction with Phe360, Phe403, and Phe398. MD result demonstrated that nonpolar term of compound 3881 made great contributions to binding affinities. It showed an IC50 being 2.49 μM against AtHPPD in vitro. The results provided useful information for developing novel HPPD inhibitors, leading to further understanding of the interaction mechanism of HPPD inhibitors.

show abstract

Section: Resultsmentioning

confidence: 99%

Combination of Virtual Screening Protocol by in Silico toward the Discovery of Novel 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors

Sun

et al. 2018

Front. Chem.

View full text Add to dashboard Cite

show abstract

“…Structure-based virtual screening methods (Siddiquee et al, 2007) are important during the early stages of drug discovery, as they can screen compound databases using the active sites of proteins with known 3D structure (Gogoi et al, 2016). The ZINC15 database (Irwin and Shoichet, 2005) is an open source database and contains available chemical compound database (like the FDA database) prepared for virtual screening.…”

Section: Methodsmentioning

confidence: 99%

Discovery of Potential Anti-infective Therapy Targeting Glutamine Synthetase in Staphylococcus xylosus

Cui

Wang

et al. 2019

Front. Chem.

View full text Add to dashboard Cite

Glutamine synthetase (GS), which catalyzes the production of glutamine, plays essential roles in most biological growth and biofilm formation, suggesting that GS may be used as a promising target for antibacterial therapy. We asked whether a GS inhibitor could be found as an anti-infective agent of Staphylococcus xylosus ( S. xylosus ). Here, computational prediction followed by experimental testing was used to characterize GS. Sorafenib was finally determined through computational prediction. In vitro experiments showed that sorafenib has an inhibitory effect on the growth of S. xylosus by competitively occupying the active site of GS, and the minimum inhibitory concentration was 4 mg/L. In vivo experiments also proved that treatment with sorafenib significantly reduced the levels of TNF-α and IL-6 in breast tissue from mice mastitis, which was further confirmed by histopathology examination. These findings indicated that sorafenib could be utilized as an anti-infective agent for the treatment of infections caused by S. xylosus .

show abstract

“…Test sets including active compounds and inactive compounds was prepared using the same protocol as the training set preparation and used to determine whether the hypothesis was able to discern active compounds. Fit value was used as an important evaluation criterion [ 32 ].…”

Section: Methodsmentioning

confidence: 99%

3D Pharmacophore-Based Virtual Screening and Docking Approaches toward the Discovery of Novel HPPD Inhibitors

Sun

et al. 2017

Molecules

View full text Add to dashboard Cite

p-Hydroxyphenylpyruvate dioxygenase (HPPD) is not only the useful molecular target in treating life-threatening tyrosinemia type I, but also an important target for chemical herbicides. A combined in silico structure-based pharmacophore and molecular docking-based virtual screening were performed to identify novel potential HPPD inhibitors. The complex-based pharmacophore model (CBP) with 0.721 of ROC used for screening compounds showed remarkable ability to retrieve known active ligands from among decoy molecules. The ChemDiv database was screened using CBP-Hypo2 as a 3D query, and the best-fit hits subjected to molecular docking with two methods of LibDock and CDOCKER in Accelrys Discovery Studio 2.5 (DS 2.5) to discern interactions with key residues at the active site of HPPD. Four compounds with top rankings in the HipHop model and well-known binding model were finally chosen as lead compounds with potential inhibitory effects on the active site of target. The results provided powerful insight into the development of novel HPPD inhibitors herbicides using computational techniques.

show abstract

3D pharmacophore-based virtual screening, docking and density functional theory approach towards the discovery of novel human epidermal growth factor receptor-2 (HER2) inhibitors

Cited by 21 publications

References 83 publications

Combination of Virtual Screening Protocol by in Silico toward the Discovery of Novel 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors

Combination of Virtual Screening Protocol by in Silico toward the Discovery of Novel 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors

Discovery of Potential Anti-infective Therapy Targeting Glutamine Synthetase in Staphylococcus xylosus

3D Pharmacophore-Based Virtual Screening and Docking Approaches toward the Discovery of Novel HPPD Inhibitors

Contact Info

Product

Resources

About