Combined Ligand/Structure-Based Virtual Screening and Molecular Dynamics Simulations of Steroidal Androgen Receptor Antagonists

doi:10.1155/2017/3572394

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	Combined Ligand/Structure-Based Virtual Screening and Molecular Dynamics Simulations of Steroidal Androgen Receptor Antagonists
	Wang, YW; Han, R; Zhang, HM; Liu, HL; Li, JZ; Liu, HX; Gramatica, P; Li, JZ (reprint author), Lanzhou Univ, Sch Pharm, 199 West Donggang Rd, Lanzhou 730000, Peoples R China.
刊名	BIOMED RESEARCH INTERNATIONAL
	2017
ISSN号	2314-6133
DOI	10.1155/2017/3572394
文献子类	Article
英文摘要	Theantiandrogens, 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 7 alpha-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.
学科主题	Biotechnology & Applied Microbiology ; Research & Experimental Medicine
出版地	LONDON
资助项目	国家自然科学基金项目 ; 中央高校基本科研业务费专项资金
项目编号	National Natural Science Foundation of China [21205055] ; Fundamental Research Funds for the Central Universities [lzujbky-2015-310]
语种	英语
WOS记录号	WOS:000395160600001
资助机构	NSFC ; LZU
内容类型	期刊论文
源URL	[http://ir.lzu.edu.cn/handle/262010/189100]
专题	药学院_期刊论文
通讯作者	Li, JZ (reprint author), Lanzhou Univ, Sch Pharm, 199 West Donggang Rd, Lanzhou 730000, Peoples R China.
推荐引用方式 GB/T 7714	Wang, YW,Han, R,Zhang, HM,et al. Combined Ligand/Structure-Based Virtual Screening and Molecular Dynamics Simulations of Steroidal Androgen Receptor Antagonists[J]. BIOMED RESEARCH INTERNATIONAL,2017.
APA	Wang, YW.,Han, R.,Zhang, HM.,Liu, HL.,Li, JZ.,...&Li, JZ .(2017).Combined Ligand/Structure-Based Virtual Screening and Molecular Dynamics Simulations of Steroidal Androgen Receptor Antagonists.BIOMED RESEARCH INTERNATIONAL.
MLA	Wang, YW,et al."Combined Ligand/Structure-Based Virtual Screening and Molecular Dynamics Simulations of Steroidal Androgen Receptor Antagonists".BIOMED RESEARCH INTERNATIONAL (2017).