Combined LigandStructure-Based Virtual Screening and Molecular Dynamics Simulations of Steroidal Androgen Receptor Antagonists
Joint Authors
Liu, Huan-Xiang
Wang, Yuwei
Han, Rui
Zhang, Huimin
Liu, Hongli
Li, Jiazhong
Gramatica, Paola
Source
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-18, 18 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-02-15
Country of Publication
Egypt
No. of Pages
18
Main Subjects
Abstract EN
The antiandrogens, such as bicalutamide, targeting the androgen receptor (AR), are the main endocrine therapies for prostate cancer (PCa).
But as drug resistance to antiandrogens emerges in advanced PCa, there presents a high medical need for exploitation of novel AR antagonists.
In this work, the relationships between the molecular structures and antiandrogenic activities of a series of 7α-substituted dihydrotestosterone derivatives were investigated.
The proposed MLR model obtained high predictive ability.
The thoroughly validated QSAR model was used to virtually screen new dihydrotestosterones derivatives taken from PubChem, resulting in the finding of novel compounds CID_70128824, CID_70127147, and CID_70126881, whose in silico bioactivities are much higher than the published best one, even higher than bicalutamide.
In addition, molecular docking, molecular dynamics (MD) simulations, and MM/GBSA have been employed to analyze and compare the binding modes between the novel compounds and AR.
Through the analysis of the binding free energy and residue energy decomposition, we concluded that the newly discovered chemicals can in silico bind to AR with similar position and mechanism to the reported active compound and the van der Waals interaction is the main driving force during the binding process.
American Psychological Association (APA)
Wang, Yuwei& Han, Rui& Zhang, Huimin& Liu, Hongli& Li, Jiazhong& Liu, Huan-Xiang…[et al.]. 2017. Combined LigandStructure-Based Virtual Screening and Molecular Dynamics Simulations of Steroidal Androgen Receptor Antagonists. BioMed Research International،Vol. 2017, no. 2017, pp.1-18.
https://search.emarefa.net/detail/BIM-1136100
Modern Language Association (MLA)
Wang, Yuwei…[et al.]. Combined LigandStructure-Based Virtual Screening and Molecular Dynamics Simulations of Steroidal Androgen Receptor Antagonists. BioMed Research International No. 2017 (2017), pp.1-18.
https://search.emarefa.net/detail/BIM-1136100
American Medical Association (AMA)
Wang, Yuwei& Han, Rui& Zhang, Huimin& Liu, Hongli& Li, Jiazhong& Liu, Huan-Xiang…[et al.]. Combined LigandStructure-Based Virtual Screening and Molecular Dynamics Simulations of Steroidal Androgen Receptor Antagonists. BioMed Research International. 2017. Vol. 2017, no. 2017, pp.1-18.
https://search.emarefa.net/detail/BIM-1136100
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1136100