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结构基因组学的靶点选择:综述

Target selection for structural genomics: an overview.

作者信息

Marsden Russell L, Orengo Christine A

机构信息

Biochemistry and Molecular Biology Department, University College London, London, UK.

出版信息

Methods Mol Biol. 2008;426:3-25. doi: 10.1007/978-1-60327-058-8_1.

Abstract

The success of the whole genome sequencing projects brought considerable credence to the belief that high-throughput approaches, rather than traditional hypothesis-driven research, would be essential to structurally and functionally annotate the rapid growth in available sequence data within a reasonable time frame. Such observations supported the emerging field of structural genomics, which is now faced with the task of providing a library of protein structures that represent the biological diversity of the protein universe. To run efficiently, structural genomics projects aim to define a set of targets that maximize the potential of each structure discovery whether it represents a novel structure, novel function, or missing evolutionary link. However, not all protein sequences make suitable structural genomics targets: It takes considerably more effort to determine the structure of a protein than the sequence of its gene because of the increased complexity of the methods involved and also because the behavior of targeted proteins can be extremely variable at the different stages in the structural genomics "pipeline." Therefore, structural genomics target selection must identify and prioritize the most suitable candidate proteins for structure determination, avoiding "problematic" proteins while also ensuring the ultimate goals of the project are followed.

摘要

全基因组测序项目的成功使人们更加坚信,高通量方法而非传统的假设驱动研究,对于在合理的时间框架内对可用序列数据的快速增长进行结构和功能注释至关重要。这些观察结果支持了结构基因组学这一新兴领域,该领域目前面临着提供一个代表蛋白质世界生物多样性的蛋白质结构库的任务。为了高效运行,结构基因组学项目旨在定义一组目标,以最大限度地发挥每个结构发现的潜力,无论其代表新结构、新功能还是缺失的进化联系。然而,并非所有蛋白质序列都适合作为结构基因组学的目标:由于所涉及方法的复杂性增加,以及目标蛋白质在结构基因组学“流程”的不同阶段行为可能极其多变,确定蛋白质的结构比确定其基因序列要付出更多努力。因此,结构基因组学目标选择必须识别最合适的候选蛋白质并确定其优先级,以进行结构测定,避免选择“有问题”的蛋白质,同时还要确保遵循项目的最终目标。

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