Improving the quality of 3D-QSAR by using flexible-ligand receptor models

CORC > 过程工程研究所 > 中国科学院过程工程研究所 > 研究所（批量导入）

	Improving the quality of 3D-QSAR by using flexible-ligand receptor models
	Pei, JF ; Chen, H ; Liu, ZM ; Han, XF ; Wang, Q ; Shen, B ; Zhou, JJ ; Lai, LH
刊名	JOURNAL OF CHEMICAL INFORMATION AND MODELING
	2005-11-01
卷号	45 期号:6 页码:1920-1933
关键词	gamma-aminobutyric-acid binding free-energy pseudoreceptor models surface models construction inhibitors alignment 4d-qsar qsar representation
ISSN号	1549-9596
其他题名	J. Chem Inf. Model.
中文摘要	To address the problems associated with molecular conformations and alignments in the 3D-QSAR studies, we have developed the Flexible Ligand - Atomic Receptor Model (FLARM) 2.0 method. The FLARM 2.0 method has three unique features as compared to other pseudoreceptor model methods: (1) the training ligands are flexibly optimized inside the receptors to achieve minimal docking energies; (2) the receptor atoms are spatially moveable in the process of genetic evolving in order to avoid improper initial receptor shapes; and (3) void receptor sites are specially favored in order to obtain open receptor models that allow large gaps. Advantages of an open model include less noise information, a smaller risk of overfitting, and ease of locating the key interaction sites. The latter two features, inherited from the previous FLARM 1.0 method, can improve the predictive ability of the 3D-QSAR models, while the first feature is newly implemented to relieve the uncertainty caused by improper conformation and alignment. Three FLARM 2.0 case studies were performed, and the results show that FLARM 2.0 models are highly predictive and robust. FLARM 2.0 pseudoreceptor models can correspond well with the pharmacophore models and/or the binding sites of the real protein receptors.
英文摘要	To address the problems associated with molecular conformations and alignments in the 3D-QSAR studies, we have developed the Flexible Ligand - Atomic Receptor Model (FLARM) 2.0 method. The FLARM 2.0 method has three unique features as compared to other pseudoreceptor model methods: (1) the training ligands are flexibly optimized inside the receptors to achieve minimal docking energies; (2) the receptor atoms are spatially moveable in the process of genetic evolving in order to avoid improper initial receptor shapes; and (3) void receptor sites are specially favored in order to obtain open receptor models that allow large gaps. Advantages of an open model include less noise information, a smaller risk of overfitting, and ease of locating the key interaction sites. The latter two features, inherited from the previous FLARM 1.0 method, can improve the predictive ability of the 3D-QSAR models, while the first feature is newly implemented to relieve the uncertainty caused by improper conformation and alignment. Three FLARM 2.0 case studies were performed, and the results show that FLARM 2.0 models are highly predictive and robust. FLARM 2.0 pseudoreceptor models can correspond well with the pharmacophore models and/or the binding sites of the real protein receptors.
WOS标题词	Science & Technology ; Life Sciences & Biomedicine ; Physical Sciences ; Technology
类目[WOS]	Chemistry, Medicinal ; Chemistry, Multidisciplinary ; Computer Science, Information Systems ; Computer Science, Interdisciplinary Applications
研究领域[WOS]	Pharmacology & Pharmacy ; Chemistry ; Computer Science
关键词[WOS]	GAMMA-AMINOBUTYRIC-ACID ; BINDING FREE-ENERGY ; PSEUDORECEPTOR MODELS ; SURFACE MODELS ; CONSTRUCTION ; INHIBITORS ; ALIGNMENT ; 4D-QSAR ; QSAR ; REPRESENTATION
收录类别	SCI
原文出处	://WOS:000233689400057
语种	英语
WOS记录号	WOS:000233689400057
公开日期	2013-10-25
内容类型	期刊论文
版本	出版稿
源URL	[http://ir.ipe.ac.cn/handle/122111/4179]
专题	过程工程研究所_研究所（批量导入）
作者单位	1.Peking Univ, Coll Chem & Mol Engn, Beijing 100871, Peoples R China 2.Peking Univ, State Key Lab Struct Chem Stable & Unstable Speci, Coll Med, Beijing 100871, Peoples R China 3.Peking Univ, Ctr Theoret Biol, Beijing 100871, Peoples R China 4.Chinese Acad Sci, Comp Network Informat Ctr, Beijing 100080, Peoples R China 5.Chinese Acad Sci, Inst Proc Engn, Beijing 100080, Peoples R China
推荐引用方式 GB/T 7714	Pei, JF,Chen, H,Liu, ZM,et al. Improving the quality of 3D-QSAR by using flexible-ligand receptor models[J]. JOURNAL OF CHEMICAL INFORMATION AND MODELING,2005,45(6):1920-1933.
APA	Pei, JF.,Chen, H.,Liu, ZM.,Han, XF.,Wang, Q.,...&Lai, LH.(2005).Improving the quality of 3D-QSAR by using flexible-ligand receptor models.JOURNAL OF CHEMICAL INFORMATION AND MODELING,45(6),1920-1933.
MLA	Pei, JF,et al."Improving the quality of 3D-QSAR by using flexible-ligand receptor models".JOURNAL OF CHEMICAL INFORMATION AND MODELING 45.6(2005):1920-1933.