title: Computational models for predicting interactions with membrane transporters.
abstract: 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.
authors: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, China.
authors: Y
authors: Y
authors: Xu
authors: Q
authors: Q
authors: Shen
authors: X
authors: X
authors: Liu
authors: J
authors: J
authors: Lu
authors: S
authors: S
authors: Li
authors: C
authors: C
authors: Luo
authors: L
authors: L
authors: Gong
authors: X
authors: X
authors: Luo
authors: M
authors: M
authors: Zheng
authors: H
authors: H
authors: Jiang
mesh_terms: D000818:Animals; D003198:Computer Simulation; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D021281:Quantitative Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D026901:Membrane Transport Proteins