scholarly journals Retrospective Validation of a Structure-Based Virtual Screening Protocol to Identify Ligands for Estrogen Receptor Alpha and Its Application to Identify the Alpha-Mangostin Binding Pose

2014 ◽  
Vol 14 (2) ◽  
pp. 103-108
Author(s):  
Agustina Setiawati ◽  
Florentinus Dika Octa Riswanto ◽  
Sri Hartati Yuliani ◽  
Enade Perdana Istyastono
Keyword(s):  
Estrogen Receptor ◽  
Virtual Screening ◽  
Area Under Curve ◽  
Estrogen Receptor Alpha ◽  
Binding Pocket ◽  
Receiver Operator Characteristic ◽  
Garcinia Mangostana ◽  
Receptor Alpha ◽  
Screening Protocol ◽  
Auc Value

The publicly available enhanced data of ligands and decoys for estrogen receptor alpha (ERα) which were recently published has made the retrospective validation of a structure-based virtual screening (SBVS) protocol to identify ligands for ERα possible. In this article, we present the retrospective validation of an SBVS protocol using PLANTS molecular docking software version 1.2 (PLANTS1.2) as the backbone software. The protocol shows better enrichment factor at 1% false positives (EF1%) value and the Area Under Curve (AUC) value of the Receiver Operator Characteristic (ROC) compared to the original published protocol. Moreover, in all 1000 iterative attempts the protocol could reproduce the co-crystal pose of 4-hydroxitamoxifen in ERα binding pocket. It shows that the protocol is not only able to identify potent ligands for ERα but also able to be employed in examining binding pose of known ligand. Thence, the protocol was successfully employed to examine the binding poses of α-mangostin, an ERα ligand found in the Garcinia mangostana, L. pericarp.

‘tieredScreen’ - Layered Virtual Screening Tool for the Identification of Novel Estrogen Receptor Alpha Modulators

2010 ◽  
Vol 29 (5) ◽  
pp. 421-430 ◽  
Author(s):  
Yidong Yang ◽  
Giorgio Carta ◽  
Martin B. Peters ◽  
Trevor Price ◽  
Niamh O'Boyle ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Virtual Screening ◽  
Estrogen Receptor Alpha ◽  
Screening Tool ◽  
Receptor Alpha

The nature of the ligand-binding pocket of estrogen receptor alpha and beta: The search for subtype-selective ligands and implications for the prediction of estrogenic activity

2003 ◽  
Vol 75 (11-12) ◽  
pp. 2397-2403 ◽  
Author(s):  
J. A. Katzenellenbogen ◽  
R. Muthyala ◽  
B. S. Katzenellenbogen
Keyword(s):  
Estrogen Receptor ◽  
Ligand Binding ◽  
Estrogen Receptor Alpha ◽  
Estrogenic Activity ◽  
Binding Pocket ◽  
Receptor Alpha ◽  
Subtype Selectivity ◽  
Selective Ligands ◽  
Binding Pockets ◽  
Subtype Selective

The ligand-binding pockets of estrogen receptor alpha and beta (ERα and ERβ) appear to have subpockets of different size and flexibility. To find ligands that will discriminate between the two ER subtypes on the basis of affinity or efficacy, we have prepared compounds of varying size, shape and structure. We have evaluated the binding affinity of these compounds and their potency and efficacy as transcriptional activators through ERα and ERβ. In this manner, we have identified a number of ligands that show pronounced ER subtype selectivity. These studies also highlight the eclectic structure–activity relationships of estrogens and the challenges inherent in developing computational methods for the prediction of estrogenic activity.

scholarly journals Effect of single mutagenesis on the binding pocket of canine estrogen receptor alpha: Structure and binding affinity

2016 ◽  
Vol 2 (2) ◽  
pp. 116 ◽  
Author(s):  
Waraphan Toniti ◽  
Aekkapot Chamkasem ◽  
Panpanga Sangsuriya ◽  
Pranom Puchadapirom
Keyword(s):  
Hydrogen Bond ◽  
Estrogen Receptor ◽  
Estrogen Receptor Alpha ◽  
Estrogen Therapy ◽  
Binding Pocket ◽  
Single Mutation ◽  
Hydrogen Bond Interaction ◽  
Receptor Alpha ◽  
Bond Interaction

Hormone-related mammary gland tumors are among the most commonly diagnosed neoplasms in female dogs. Estrogen enacts its biological roles through specific receptors known as estrogen receptors (ER). In human medicine, anti-estrogen therapy has become the gold standard in ER-positive breast tumors’ therapeutic regimen. The binding pocket of the canine estrogen receptor alpha (cERα) ligand binding domain comprises of three key amino acid residues including E354, G522 and L526, which stabilize the cERα-E2 interaction via hydrogen bonding. The side chain of E354 shares hydrogen bond interaction with the A ring of its natural ligand E2, whereas the main chain of G522 and L526 interact with the E2-D ring. The single mutation of the E354 aberrant, along with the hydrogen bond interaction between cERα and both ligands, leads to a variety of binding affinities. According to this <em>in silico</em> model, it may be concluded that E354 plays a role in the cERα activities. The effects of single mutants might need to be studied further <em>in vitro</em> and <em>in vivo</em>.

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