Molecular docking and molecular dynamics simulation studies of GPR40 receptor–agonist interactions

Lu, Shaoyong; Jiang, Yong‐Jun; Lv, Jing; Wu, Tingfeng; Q, Yu; Zhu, Weiliang

doi:10.1016/j.jmgm.2010.02.001

Cited by 83 publications

(45 citation statements)

References 37 publications

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“…The grid center was defined at the center of ligands in the co-crystal structures of GSK3β/CDK5. The Lamarckian genetic algorithm was used for ligand conformational search; the parameters were set the same in our previous studies [20][21][22][23]. Fifty independent docking runs were carried out.…”

Section: Molecular Dockingmentioning

confidence: 99%

Structural basis of valmerins as dual inhibitors of GSK3β/CDK5

Wang

Tian

et al. 2014

J Mol Model

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Development of multi-target drugs is becoming increasingly attractive in the repertoire of protein kinase inhibitors discovery. In this study, we carried out molecular docking, molecular dynamics simulations, molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) binding free energy calculations, principal component analysis (PCA), and dynamical cross-correlation matrices (DCCM) to dissect the molecular mechanism for the valmerin-19 acting as a dual inhibitor for glycogen synthase kinase 3β (GSK3β) and cyclin-dependent kinase 5 (CDK5). Detailed MM-PBSA calculations revealed that the binding free energies of the valmerin-19 to GSK3β/CDK5 were calculated to be -12.60 ± 2.28 kcal mol(-1) and -11.85 ± 2.54 kcal mol(-1), respectively, indicating that valmerin-19 has the potential to act as a dual inhibitor of GSK3β/CDK5. The analyses of PCA and DCCM results unraveled that binding of the valmerin-19 reduced the conformational dynamics of GSK3β/CDK5 and the valmerin-19 bound to GSK3β/CDK5 might occur mostly through a conformational selection mechanism. This study may be helpful for the future design of novel and potent dual GSK3β/CDK5 inhibitors.

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Section: Molecular Dockingmentioning

confidence: 99%

Structural basis of valmerins as dual inhibitors of GSK3β/CDK5

Wang

Tian

et al. 2014

J Mol Model

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“…DGLA binding to GPR40 was found to be stabilized through the formation of hydrogen bonds with Tyr91, Arg183, and Arg258, whereas a previous study of GPR40 with the agonist GW9508 reported hydrogen bonding to Asn244 and Ser247 [25]. This discrepancy may result from differences in the model systems; e.g., 4PHU (the crystal structure of human GPR40 bound to the allosteric agonist TAK-875) versus 1GZM (the structure of bovine rhodopsin in a trigonal crystal form).…”

Section: Discussionmentioning

confidence: 74%

Discovery of a novel effect of electric field exposure on human plasma beta-endorphin and interleukin-12 levels: Insight into mechanisms of pain alleviation and defense against infection by electric field therapy

2015

Integr Mol Med

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Medical treatment using high-voltage electric potential (HELP) devices to generate an electric field (EF) is an alternative therapy commonly used in Japan, but the molecular mechanisms involved are poorly understood. Healthy human subjects were exposed to a single 15 min 18 kV stimulation of HELP, after which plasma concentrations of several peptide hormones and cytokines were examined at 0, 15, and 45 min time points using enzyme-linked immunosorbent assays (ELISA). β-Endorphin, alpha-melanocyte-stimulating hormone (α-MSH), glucagon-like peptide-1 (GLP-1), interleukin (IL)-4, IL-12, and interferon-gamma (IFN-γ) levels were significantly up-regulated after HELP exposure. Under these conditions, HELP exposure had no effect on corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), IL-6, or IL-10 levels. Because HELP exposure is known to induce up-regulation of cis-8,11,14-eicosatrienoic acid (dihomo-γ-linolenic acid; DGLA), we examined the effect of DGLA on β-endorphin secretion. In human epidermal keratinocytes, DGLA significantly induced the secretion of β-endorphins, but not α-MSH. DGLA-induced β-endorphin secretion was sensitive to the G protein-coupled receptor (GPR) 40 antagonist GW1100. Our findings provide new insights into the molecular mechanisms of pain control and defense against infection induced by EF therapy.

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“…RMSD cluster analysis and binding free energy evaluations were used to find the best binding mode of ligand position. The final binding free energy is based on intermolecular energy, internal energy of ligand, and torsional free energy (Lu et al, 2010). Visualization of the docking results by VMD approved that all ligands are docked successfully into the active site.…”

Section: Autodock Binding Affinities Of the Azo Dyes Into Azrc Proteinmentioning

confidence: 99%

A novel recombinant AzrC protein proposed by molecular docking and in silico analyses to improve azo dye's binding affinity

Dehghanian

Kay

Kahrizi

2015

Gene

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Molecular docking and molecular dynamics simulation studies of GPR40 receptor–agonist interactions

Cited by 83 publications

References 37 publications

Structural basis of valmerins as dual inhibitors of GSK3β/CDK5

Structural basis of valmerins as dual inhibitors of GSK3β/CDK5

Discovery of a novel effect of electric field exposure on human plasma beta-endorphin and interleukin-12 levels: Insight into mechanisms of pain alleviation and defense against infection by electric field therapy

A novel recombinant AzrC protein proposed by molecular docking and in silico analyses to improve azo dye's binding affinity

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