An integrated approach to knowledge-driven structure-based virtual screening

Henzler, Angela M.; Urbaczek, Sascha; Hilbig, Matthias; Rarey, Matthias

doi:10.1007/s10822-014-9769-4

Cited by 20 publications

(16 citation statements)

References 39 publications

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“…The ligands were docked in the presence of metal ion cofactors and structurally relevant water molecules into the active-site clefts of the receptors using the JAMDA web server [40][41][42]. The appropriate protonation states and hydrogen atom coordinates were assigned to the receptors prior to docking using the integrated Protoss optimization tool [43].…”

Section: Receptor-ligand Dockingmentioning

confidence: 99%

In Vitro and In Silico Evaluation of ACE2 and LOX Inhibitory Activity of Origanum Essential Oils and Carvacrol

Demirci

Teralı²,

Karadağ

et al. 2022

Planta Med

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Origanum spp. are used both for culinary purposes and for their biological activities. In this study, commercially Origanum majorana, O. minutiflorum, O. vulgare, and O. onites essential oils, and their prominent constituent carvacrol was evaluated for their in vitro and in silico angiotensin-converting enzyme 2 (ACE2) and lipoxygenase (LOX) enzyme inhibitory potentials. The essential oils were analysed by GC-FID and GC/MS, where carvacrol was identified as the major component (62–81%), confirming the quality. In vitro enzyme inhibition assays were conducted both with the essential oils (20 µg/mL) and with carvacrol (5 µg/mL). The comparative values of ACE2 percent inhibition for O. majorana, O. minutiflorum, O. vulgare and O. onites essential oils were determined as 85.5%, 79.1%, 74.3% and 42.8%, respectively. As a result of the enzyme assays, carvacrol showed 90.7% in vitro ACE2 inhibitory activity. The in vitro LOX inhibition of the essential oils (in the same order) was 89.4%, 78.9%, 81.1%, and 73.5%, respectively, where carvacrol showed 74.8% inhibition. In addition, protein–ligand docking, and interaction profiling was used to gain structural and mechanistic insights into the ACE2 and LOX inhibitory potentials of major Origanum essential oil constituents. The in silico findings agreed with the significant enzyme inhibition activity observed in vitro. Further in vivo studies are suggested to confirm the safety and efficacy of the oils.

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Section: Receptor-ligand Dockingmentioning

confidence: 99%

In Vitro and In Silico Evaluation of ACE2 and LOX Inhibitory Activity of Origanum Essential Oils and Carvacrol

Demirci

Teralı²,

Karadağ

et al. 2022

Planta Med

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“…JAMDA docking combines the TrixX docking algorithm ( 12 , 13 ) for initial pose generation with the JAMDA scoring function ( 14 ), and our novel LSL-BFGS optimization algorithm( 14 , 15 ) for scoring and pose optimization. Initially, conformers for the molecule to be docked are generated with the Conformator ( 11 ).…”

Section: Materials and Methods: Extensions And Novel Toolsmentioning

confidence: 99%

ProteinsPlus: a comprehensive collection of web-based molecular modeling tools

Schöning-Stierand

Diedrich

Ehrt

et al. 2022

Nucleic Acids Research

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Upon the ever-increasing number of publicly available experimentally determined and predicted protein and nucleic acid structures, the demand for easy-to-use tools to investigate these structural models is higher than ever before. The ProteinsPlus web server (https://proteins.plus) comprises a growing collection of molecular modeling tools focusing on protein–ligand interactions. It enables quick access to structural investigations ranging from structure analytics and search methods to molecular docking. It is by now well-established in the community and constantly extended. The server gives easy access not only to experts but also to students and occasional users from the field of life sciences. Here, we describe its recently added new features and tools, beyond them a novel method for on-the-fly molecular docking and a search method for single-residue substitutions in local regions of a protein structure throughout the whole Protein Data Bank. Finally, we provide a glimpse into new avenues for the annotation of AlphaFold structures which are directly accessible via a RESTful service on the ProteinsPlus web server.

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“…Missing hydrogen atoms were added to the structures using Protoss [ 99 , 100 ], available at , accessed on 23 July 2021. The ligands were docked in the presence of cofactors and structurally relevant water molecules into the inhibitor-binding pockets of the proteins using JAMDA [ 101 , 102 , 103 ], available at , accessed on 23 July 2021. Each docking site was defined by the cocrystallized inhibitor, with a site radius of 6.5 Å. Protein–ligand docking was executed with high precision.…”

Section: Methodsmentioning

confidence: 99%

Isolation, Characterization and In Silico Studies of Secondary Metabolites from the Whole Plant of Polygala inexpectata Peşmen & Erik

et al. 2022

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Polygala species are frequently used worldwide in the treatment of various diseases, such as inflammatory and autoimmune disorders as well as metabolic and neurodegenerative diseases, due to the large number of secondary metabolites they contain. The present study was performed on Polygala inexpectata, which is a narrow endemic species for the flora of Turkey, and resulted in the isolation of nine known compounds, 6,3′-disinapoyl-sucrose (1), 6-O-sinapoyl,3′-O-trimethoxy-cinnamoyl-sucrose (tenuifoliside C) (2), 3′-O-(O-methyl-feruloyl)-sucrose (3), 3′-O-(sinapoyl)-sucrose (4), 3′-O-trimethoxy-cinnamoyl-sucrose (glomeratose) (5), 3′-O-feruloyl-sucrose (sibiricose A5) (6), sinapyl alcohol 4-O-glucoside (syringin or eleutheroside B) (7), liriodendrin (8), and 7,4′-di-O-methylquercetin-3-O-β-rutinoside (ombuin 3-O-rutinoside or ombuoside) (9). The structures of the compounds were determined by the spectroscopic methods including 1D-NMR (1H NMR, 13C NMR, DEPT-135), 2D-NMR (COSY, NOESY, HSQC, HMBC), and HRMS. The isolated compounds were shown in an in silico setting to be accommodated well within the inhibitor-binding pockets of myeloperoxidase and inducible nitric oxide synthase and anchored mainly through hydrogen-bonding interactions and π-effects. It is therefore plausible to suggest that the previously established anti-inflammatory properties of some Polygala-derived phytochemicals may be due, in part, to the modulation of pro-inflammatory enzyme activities.

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An integrated approach to knowledge-driven structure-based virtual screening

Cited by 20 publications

References 39 publications

In Vitro and In Silico Evaluation of ACE2 and LOX Inhibitory Activity of Origanum Essential Oils and Carvacrol

In Vitro and In Silico Evaluation of ACE2 and LOX Inhibitory Activity of Origanum Essential Oils and Carvacrol

ProteinsPlus: a comprehensive collection of web-based molecular modeling tools

Isolation, Characterization and In Silico Studies of Secondary Metabolites from the Whole Plant of Polygala inexpectata Peşmen & Erik

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