Computational Models for Predicting Interactions with Membrane Transporters

doi:10.2174/0929867311320160005

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	Computational Models for Predicting Interactions with Membrane Transporters
	Xu, Y.2; Shen, Q.2; Liu, X.2 ; Lu, J.2; Li, S.2; Luo, C.2 ; Gong, L.1; Luo, X.2; Zheng, M.2; Jiang, H.2
刊名	CURRENT MEDICINAL CHEMISTRY
	2013-05
卷号	20 期号:16 页码:2118-2136
关键词	Computational methods homology modeling membrane transporter phamacophore models QSAR models supervised/unsupervised learning algorithms
ISSN号	0929-8673
DOI	10.2174/0929867311320160005
文献子类	Article
英文摘要	Membrane transporters, including two members: ATP-binding cassette (ABC) transporters and solute carrier (SLC) transporters are proteins that play important roles to facilitate molecules into and out of cells. Consequently, these transporters can be major determinants of the therapeutic efficacy, toxicity and pharmacokinetics of a variety of drugs. Considering the time and expense of bio-experiments taking, research should be driven by evaluation of efficacy and safety. Computational methods arise to be a complementary choice. In this article, we provide an overview of the contribution that computational methods made in transporters field in the past decades. At the beginning, we present a brief introduction about the structure and function of major members of two families in transporters. In the second part, we focus on widely used computational methods in different aspects of transporters research. In the absence of a high-resolution structure of most of transporters, homology modeling is a useful tool to interpret experimental data and potentially guide experimental studies. We summarize reported homology modeling in this review. Researches in computational methods cover major members of transporters and a variety of topics including the classification of substrates and/or inhibitors, prediction of protein-ligand interactions, constitution of binding pocket, phenotype of non-synonymous single-nucleotide polymorphisms, and the conformation analysis that try to explain the mechanism of action. As an example, one of the most important transporters P-gp is elaborated to explain the differences and advantages of various computational models. In the third part, the challenges of developing computational methods to get reliable prediction, as well as the potential future directions in transporter related modeling are discussed.
资助项目	State Key Laboratory of Drug Research[00000000] ; State Key Program of Basic Research of China[2009CB918502] ; National Natural Science Foundation of China[81001399] ; National Natural Science Foundation of China[21021063] ; National Natural Science Foundation of China[81230076] ; National Natural Science Foundation of China[21210003] ; National ST Major Project[2012ZX09301-001-002] ; National ST Major Project[2012ZX09301-001-006] ; Hi-Tech Research and Development Program of China[SS2012AA021103] ; Hi-TECH Research and Development Program of China[2012AA020308]
WOS关键词	CANCER RESISTANCE PROTEIN ; ORGANIC ANION TRANSPORTERS ; P-GLYCOPROTEIN INHIBITORS ; H+/ORGANIC CATION ANTIPORTER ; MULTIDRUG EFFLUX PROTEIN ; RETRACTED ARTICLE. SEE ; KIDNEY 293 CELLS ; ABC TRANSPORTER ; MOLECULAR-CLONING ; ESCHERICHIA-COLI
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy
语种	英语
出版者	BENTHAM SCIENCE PUBL LTD
WOS记录号	WOS:000317662200005
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277641]
专题	药物安全性评价中心中科院受体结构与功能重点实验室新药研究国家重点实验室药物发现与设计中心
通讯作者	Gong, L.
作者单位	1.Chinese Acad Sci, Ctr Drug Safety & Evaluat Res, State Key Lab Drug Res, Shanghai Inst Mat Med, Beijing 100864, Peoples R China 2.Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, Beijing 100864, Peoples R China;
推荐引用方式 GB/T 7714	Xu, Y.,Shen, Q.,Liu, X.,et al. Computational Models for Predicting Interactions with Membrane Transporters[J]. CURRENT MEDICINAL CHEMISTRY,2013,20(16):2118-2136.
APA	Xu, Y..,Shen, Q..,Liu, X..,Lu, J..,Li, S..,...&Jiang, H..(2013).Computational Models for Predicting Interactions with Membrane Transporters.CURRENT MEDICINAL CHEMISTRY,20(16),2118-2136.
MLA	Xu, Y.,et al."Computational Models for Predicting Interactions with Membrane Transporters".CURRENT MEDICINAL CHEMISTRY 20.16(2013):2118-2136.