Discovery of novel microtubule stabilizers targeting taxane binding site by applying molecular docking, molecular dynamics simulation, and anticancer activity testing

Zhang, Hui; Qi, Hua-Zhao; Mao, Jun; Zhang, Hongrui; Luo, Qingzhi; Hu, Mei-Ling; Shen, Chen; Ding, Lei

doi:10.1016/j.bioorg.2022.105722

Cited by 5 publications

(2 citation statements)

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“…14 The hydrogen bonding played a key role in molecular recognition of interactions between a protein and ligand. 37 As can be seen from Fig. 7, the TP53 protein complexed with compound 1 and 20 could form maximum 3-4 hydrogen bonds with active site residues.…”

Section: Molecular Dynamics Simulation Evaluationmentioning

confidence: 90%

Sesquiterpenoids isolated from the rhizome of Curcuma phaeocaulis Valeton: antitumor activity, in silico molecular docking and molecular dynamics study

et al. 2023

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Section: Molecular Dynamics Simulation Evaluationmentioning

confidence: 90%

Sesquiterpenoids isolated from the rhizome of Curcuma phaeocaulis Valeton: antitumor activity, in silico molecular docking and molecular dynamics study

et al. 2023

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“…Computer-aided drug design (CADD) virtual screening has been widely used for the discovery of lead compounds with new scaffolds of specified targets from large chemical databases [ 15 , 16 ]. Among these CADD methods, the pharmacophore-based, molecular docking, and machine learning methods have been prevalently applied in the discovery of novel chemicals binding to an especial target [ 17 , 18 , 19 , 20 , 21 , 22 ]. Presently, more than 100 SGK1 inhibitors have been reported, which have provided a basis for the construction of ligand-based pharmacophore and machine learning prediction models.…”

Section: Introductionmentioning

confidence: 99%

Identification of Novel Inhibitors Targeting SGK1 via Ensemble-Based Virtual Screening Method, Biological Evaluation and Molecular Dynamics Simulation

Zhang

Shen

Zhang

et al. 2022

IJMS

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Serum and glucocorticoid-regulated kinase 1 (SGK1), as a serine threonine protein kinase of the AGC family, regulates different enzymes, transcription factors, ion channels, transporters, and cell proliferation and apoptosis. Inhibition of SGK1 is considered as a valuable approach for the treatment of various metabolic diseases. In this investigation, virtual screening methods, including pharmacophore models, Bayesian classifiers, and molecular docking, were combined to discover novel inhibitors of SGK1 from the database with 29,158 compounds. Then, the screened compounds were subjected to ADME/T, PAINS and drug-likeness analysis. Finally, 28 compounds with potential inhibition activity against SGK1 were selected for biological evaluation. The kinase inhibition activity test revealed that among these 28 hits, hit15 exhibited the highest inhibition activity against SGK1, which gave 44.79% inhibition rate at the concentration of 10 µM. In order to further investigate the interaction mechanism of hit15 and SGK1 at simulated physiological conditions, a molecular dynamics simulation was performed. The molecular dynamics simulation demonstrated that hit15 could bind to the active site of SGK1 and form stable interactions with key residues, such as Tyr178, ILE179, and VAL112. The binding free energy of the SGK1-hit15 was −48.90 kJ mol−1. Therefore, the identified hit15 with novel scaffold may be a promising lead compound for development of new SGK1 inhibitors for various diseases treatment.

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Discovery of novel S6K1 inhibitors by an ensemble-based virtual screening method and molecular dynamics simulation

Zhang

et al. 2023

J Mol Model

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Discovery of novel microtubule stabilizers targeting taxane binding site by applying molecular docking, molecular dynamics simulation, and anticancer activity testing

Cited by 5 publications

References 50 publications

Sesquiterpenoids isolated from the rhizome of Curcuma phaeocaulis Valeton: antitumor activity, in silico molecular docking and molecular dynamics study

Sesquiterpenoids isolated from the rhizome of Curcuma phaeocaulis Valeton: antitumor activity, in silico molecular docking and molecular dynamics study

Identification of Novel Inhibitors Targeting SGK1 via Ensemble-Based Virtual Screening Method, Biological Evaluation and Molecular Dynamics Simulation

Discovery of novel S6K1 inhibitors by an ensemble-based virtual screening method and molecular dynamics simulation

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