In vitro and in silico assessment of the structure-dependent binding of bisphenol analogues to glucocorticoid receptor

2017 ◽  
Vol 409 (8) ◽  
pp. 2239-2246 ◽  
Author(s):  
Jie Zhang ◽  
Tiehua Zhang ◽  
Tianzhu Guan ◽  
Hansong Yu ◽  
Tiezhu Li
Keyword(s):  
Glucocorticoid Receptor ◽  
In Silico ◽  
Bisphenol Analogues

scholarly journals Glucocorticoid resistance conferring mutation in the C-terminus of GR alters the receptor conformational dynamics

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna Kaziales ◽  
Florian Rührnößl ◽  
Klaus Richter
Keyword(s):  
Glucocorticoid Receptor ◽  
Steroid Hormones ◽  
In Silico ◽  
Conformational Dynamics ◽  
Glucocorticoid Resistance ◽  
Physiological Processes ◽  
C Terminus ◽  
Hsp90 Chaperone ◽  
In Silico Methods

AbstractThe glucocorticoid receptor is a key regulator of essential physiological processes, which under the control of the Hsp90 chaperone machinery, binds to steroid hormones and steroid-like molecules and in a rather complicated and elusive response, regulates a set of glucocorticoid responsive genes. We here examine a human glucocorticoid receptor variant, harboring a point mutation in the last C-terminal residues, L773P, that was associated to Primary Generalized Glucocorticoid Resistance, a condition originating from decreased affinity to hormone, impairing one or multiple aspects of GR action. Using in vitro and in silico methods, we assign the conformational consequences of this mutation to particular GR elements and report on the altered receptor properties regarding its binding to dexamethasone, a NCOA-2 coactivator-derived peptide, DNA, and importantly, its interaction with the chaperone machinery of Hsp90.

Use of the comprehensive in vitro proarrhythmia assay and in silico modeling to investigate the safety profile of bisphenol analogues

2020 ◽  
Vol 105 ◽  
pp. 106806
Author(s):  
Rafael Jaimes ◽  
Damon McCullough ◽  
Luther Swift ◽  
Marissa Reilly ◽  
Morgan Burke ◽  
...  
Keyword(s):  
Safety Profile ◽  
In Silico ◽  
Bisphenol Analogues ◽  
In Silico Modeling

scholarly journals In Silico Guidance for In Vitro Androgen and Glucocorticoid Receptor ToxCast Assays

2020 ◽  
Vol 54 (12) ◽  
pp. 7461-7470
Author(s):  
Timothy E. H. Allen ◽  
Mark D. Nelms ◽  
Stephen W. Edwards ◽  
Jonathan M. Goodman ◽  
Steve Gutsell ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
In Silico

scholarly journals In vitro and in silico identification of the mechanism of interaction of antimalarial drug – artemisinin with human serum albumin and genomic DNA

2019 ◽  
Author(s):  
Siranush Ginosyan ◽  
Hovakim Grabski ◽  
Susanna Tiratsuyan
Keyword(s):  
Hydrogen Bond ◽  
Human Serum Albumin ◽  
Glucocorticoid Receptor ◽  
Ligand Binding ◽  
Serum Albumin ◽  
In Silico ◽  
Genomic Dna ◽  
Mechanisms Of Action ◽  
Static Mechanism

AbstractArtemisinins are secondary metabolites of the medicinal plant Artemisia annua, which has been traditionally used in Chinese medicine. Artemisinins have anti-inflammatory, anticarcinogenic, immunomodulatory, antimicrobial, anthelmintic, antiviral, antioxidant, and other properties. Our preliminary reverse virtual screening demonstrated that the ligand-binding domain of the human glucocorticoid receptor (LBD of hGR) is the optimal target for artemisinin. At the same time, the binding sites for artemisinin with the ligand-binding domain of the human glucocorticoid receptor coincide with those of dexamethasone. However, the pharmacokinetics, pharmacodynamics, and exact molecular targets and mechanisms of action of artemisinin are not well known. In this work, the interaction of artemisinin with human serum albumin (HSA) was studied both in vitro and in silico. The results indicate that artemisinin leads to a decrease in optical absorption and quenching of fluorescence by a static mechanism, which is similar to the effect of dexamethasone. Artemisinin interacts with Drug site I on HSA and forms a hydrogen bond with arginine 218. Retardation of the genomic DNA of sarcoma S-180 cells show that artemisinin does not interact directly with DNA. On the basis of the obtained data, we proposed a hypothetical scheme of the mechanisms of action of artemisinin.HighlightsArtemisinin quenches the fluorescence of HSA by a static mechanism.Artemisinin quenches fluorescence of tryptophan.The optimized HSA structure was obtained through molecular dynamics simulations.Artemisinin binds with HSA in Drug site I and forms a hydrogen bond with Arg218.Dexamethasone binds with HSA in Drug site I and forms hydrogen bonds with Arg218, Arg222 and Va1343.A hypothetical scheme of the mechanism of action of Artemisinin was proposed.Graphical Abstract

Glucocorticoid receptor-mediated alleviation of inflammation by berberine: in vitro, in silico and in vivo investigations

2021 ◽  
Author(s):  
Yuan Liang ◽  
Tiehua Zhang ◽  
Jingqi Zhao ◽  
Chenfei Li ◽  
Haoyang Zou ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
In Silico ◽  
Biological Activities ◽  
Inflammatory Factor ◽  
Anti Inflammatory ◽  
Inflammatory Effect

As a natural dietary ingredient, berberine possesses multiple biological activities including anti-inflammatory effect. Specifically, berberine can inhibit the lipopolysaccharide-induced mRNA expressions of inflammatory factor. In this work, glucocorticoid receptor (GR)-mediated...

IN VITRO/IN SILICO CHARACTERIZATION OF ACTIVE AND PASSIVE STRESSES IN CARDIAC MUSCLE

2012 ◽  
Vol 10 (2) ◽  
pp. 171-188 ◽  
Author(s):  
Markus Boel ◽  
Oscar J. Abilez ◽  
Ahmed N Assar ◽  
Christopher K. Zarins ◽  
Ellen Kuhl
Keyword(s):  
Cardiac Muscle ◽  
In Silico ◽  
In Silico Characterization

Role of 4-O Galloylchlorogenic Acid in Lung Cancer- An Insilico Approach

2017 ◽  
Vol 9 (5) ◽  
Author(s):  
Jaynthy C. ◽  
N. Premjanu ◽  
Abhinav Srivastava
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
In Silico ◽  
Computational Study ◽  
Regulation Mechanism ◽  
Down Regulation ◽  
Fruit Extract ◽  
In Vitro Techniques ◽  
Discovery Studio

Cancer is a major disease with millions of patients diagnosed each year with high mortality around the world. Various studies are still going on to study the further mechanisms and pathways of the cancer cell proliferation. Fucosylation is one of the most important oligosaccharide modifications involved in cancer and inflammation. In cancer development increased core fucosylation by FUT8 play an important role in cell proliferation. Down regulation of FUT8 expression may help cure lung cancer. Therefore the computational study based on the down regulation mechanism of FUT8 was mechanised. Sapota fruit extract, containing 4-Ogalloylchlorogenic acid was used as the inhibitor against FUT-8 as target and docking was performed using in-silico tool, Accelrys Discovery Studio. There were several conformations of the docked result, and conformation 1 showed 80% dock score between the ligand and the target. Further the amino acids of the inhibitor involved in docking were studied using another tool, Ligplot. Thus, in-silico analysis based on drug designing parameters shows that the fruit extract can be studied further using in-vitro techniques to know its pharmacokinetics.

Discovery of New AKT1 Inhibitors by Combination of In silico Structure Based Virtual Screening Approaches and Biological Evaluations

2019 ◽  
Author(s):  
Filip Fratev ◽  
Denisse A. Gutierrez ◽  
Renato J. Aguilera ◽  
suman sirimulla
Keyword(s):  
Virtual Screening ◽  
Success Rate ◽  
Protein Interactions ◽  
In Silico ◽  
Biological Data ◽  
In Vitro Binding ◽  
Vitro Binding ◽  
Screening Protocol ◽  
Screening Approaches

AKT1 is emerging as a useful target for treating cancer. Herein, we discovered a new set of ligands that inhibit the AKT1, as shown by in vitro binding and cell line studies, using a newly designed virtual screening protocol that combines structure-based pharmacophore and docking screens. Taking together with the biological data, the combination of structure based pharamcophore and docking methods demonstrated reasonable success rate in identifying new inhibitors (60-70%) proving the success of aforementioned approach. A detail analysis of the ligand-protein interactions was performed explaining observed activities.<br>

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