Inverse docking method for new proteins targets identification: A parallel approach

Vasseur, Romain; Baud, Stéphanie; Steffenel, Luiz Angelo; Vigouroux, Xavier; Martiny, Laurent; Krajecki, Michaël; Dauchez, Manuel

doi:10.1016/j.parco.2014.09.008

Cited by 12 publications

(5 citation statements)

References 37 publications

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“…The crosslinking of these theoretical data with experimental data can further define the agonist effect of a small molecule toward a receptor. Inverse docking [ 44 ] allows for screening of a ligand on multiple receptors. In this way, it is possible to predict the preferred target of a ligand.…”

Section: Introductionmentioning

confidence: 99%

Anti-Toxoplasma gondii effect of lupane-type triterpenes from the bark of black alder (Alnus glutinosa) and identification of a potential target by reverse docking

et al. 2022

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Toxoplasmosis is a worldwide parasitosis that is generally benign. The infestation may pose a risk to immunocompromized patients and to fetuses when pregnant women have recently seroconverted. Current treatments have numerous side effects and chemoresistance is emerging, hence the need to find new anti-Toxoplasma gondii substances. This study focuses on the antiparasitic potential of lupane-type pentacyclic triterpenes isolated from the bark of black alder (Alnus glutinosa), as well as the hypothesis of their macromolecular target by an original method of reverse docking. Among the isolated triterpenes, betulone was the most active compound with an IC50 of 2.7 ± 1.2 μM, a CC50 greater than 80 μM, and a selectivity index of over 29.6. An additional study of the anti-T. gondii potential of commercially available compounds (betulonic acid methyl ester and betulonic acid) showed the important role of the C3 ketone function and the C28 oxidation level on the lupane-type triterpene in the antiparasitic activity since their IC50 and CC50 were similar to that of betulone. Finally, the most active compounds were subjected to the AMIDE reverse docking workflow. A dataset of 87 T. gondii proteins from the Protein Data Bank was created. It identified calcium-dependent protein kinase CDPK3 as the most likely target of betulin derivatives.

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Section: Introductionmentioning

confidence: 99%

Anti-Toxoplasma gondii effect of lupane-type triterpenes from the bark of black alder (Alnus glutinosa) and identification of a potential target by reverse docking

et al. 2022

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“…This, in turn, allows us to study molecular recognition and to design new bioactive compounds. 20 In this work, we propose to evaluate the susceptibility of the Zika virus to chemical compounds derived from the M. taxifolia plant due to its wide distribution in South America, particularly in Venezuela and Colombia. For this purpose, a series of compounds with affinity to NS proteins of ZIKV and DENV were identified (Figure 1).…”

Section: ■ Introductionmentioning

confidence: 99%

“…In other words, this methodology maps a series of compounds to different protein binding pockets to find the best overall compound, which then acts as a common inhibitor to several proteins. This, in turn, allows us to study molecular recognition and to design new bioactive compounds . In this work, we propose to evaluate the susceptibility of the Zika virus to chemical compounds derived from the M.…”

Section: Introductionmentioning

confidence: 99%

Inverse Molecular Docking Study of NS3-Helicase and NS5-RNA Polymerase of Zika Virus as Possible Therapeutic Targets of Ligands Derived from Marcetia taxifolia and Its Implications to Dengue Virus

et al. 2021

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Dengue and Zika are two mosquito-borne diseases of great impact on public health around the world in tropical and subtropical countries. DENV and ZIKV belong to the Flaviviridae family and the Flavivirus genus. Currently, there are no effective therapeutic agents to treat or prevent these pathologies. The main objective of this work was to evaluate potential inhibitors from active compounds obtained from Marcetia taxifolia by performing inverse molecular docking on ZIKV-NS3-helicase and ZIKV-NS5-RNA polymerase as targets. This computational strategy is based on renormalizing the binding scores of the compounds to these two proteins, allowing a direct comparison of the results across the proteins. The crystallographic structures of the ZIKV-NS3-helicase and ZIKV-NS5-RNA-polymerase proteins share a great similarity with DENV homologous proteins. The P-loop active site of the crystallographic structure of ZIKV-NS3-helicase presents a high percentage of homology with the four dengue serotypes. It was found that most ligands of the active compounds (5,3’-dihydroxy-3,6,7,8,4′-pentamethoxyflavone (5DP); 5-hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone (5HH); myricetin-3-O-rhamnoside (M3OR)) from Marcetia taxifolia had a better affinity for ZIKV-NS3-helicase than for ZIKV-NS5-RNA polymerase, as indicated by the negative multiple active site correction (MASC) score, except for M3RG that showed a higher affinity for ZIKV-NS5-RNA polymerase. On the other hand, the AutoDock Vina scores showed that M3OR had the highest score value (−9.60 kcal/mol) and the highest normalized score (1.13) against ZIKV-NS3-helicase. These results in silico demonstrated that the nonstructural proteins NS3-helicase and NS5-RNA polymerase, which share similar molecular structures between the selected viruses, could become therapeutic targets for some bioactive compounds derived from Marcetia taxifolia.

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“…These methods focused on protein-drugs (ligands) complexes to study how the drugs bind to the protein receptor, which is very important for discovering or developing new bioactive compounds in fighting against diseases. Besides, the methods for identification of protein-ligand interaction fingerprints that featuring how strong the interaction has developed as well [1][2].…”

Section: ■ Introductionmentioning

confidence: 99%

In Vitro and In Silico Studies of Quercetin and Daidzin as Selective Anticancer Agents

et al. 2021

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Quercetin and daidzin are flavonoid and flavonoid glycoside type compounds that have been found in many plants and nutraceuticals. This study aims to examine the in vitro cytotoxic and selectivity properties of quercetin and daidzin on breast and cervical cancers and to study their molecular interaction and stability on epidermal growth factor receptor tyrosine kinase (EGFR-TK) by applying molecular docking and molecular dynamics (MD) simulations. In vitro anticancer activity was performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method on breast cancer cell (T47D), cervical cancer cells (HeLa), and Vero normal cells, while molecular docking and MD simulation were done by using AutoDock Vina and Amber18 package software, respectively. Quercetin and daidzin showed potent cytotoxic and high selectivity on both cell lines. Daidzin was found to has a higher IC50 and selectivity index than quercetin. Docking and MD results showed that both compounds prefer to interact with epidermal growth factor receptor tyrosine kinase (EGFR-TK). Daidzin showed better interaction than quercetin with a docking score of -9.6 kcal/mol. Also, daidzin was found more stable than quercetin with low RMSD and RMSF values.

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Inverse docking method for new proteins targets identification: A parallel approach

Cited by 12 publications

References 37 publications

Anti-Toxoplasma gondii effect of lupane-type triterpenes from the bark of black alder (Alnus glutinosa) and identification of a potential target by reverse docking

Anti-Toxoplasma gondii effect of lupane-type triterpenes from the bark of black alder (Alnus glutinosa) and identification of a potential target by reverse docking

Inverse Molecular Docking Study of NS3-Helicase and NS5-RNA Polymerase of Zika Virus as Possible Therapeutic Targets of Ligands Derived from Marcetia taxifolia and Its Implications to Dengue Virus

In Vitro and In Silico Studies of Quercetin and Daidzin as Selective Anticancer Agents

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