Evolution of the NIGMS Protein Structure Initiative.
Evolution of the NIGMS Protein Structure Initiative.
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NIGMS 蛋白质结构计划的演变。
DOI：
10.1016/j.str.2007.11.002
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Chazin,WalterJ
中科院分区：
文献类型：
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作者：
Chazin,WalterJ
PSI目标NIGMS PSI的长期目标是使用结构基因组学方法获得蛋白质折叠空间的完整描述。正如结构基因组学一词所暗示的那样，PSI被认为是后基因组学时代的下一步。然而，PSI从根本上不同于基因组测序工作，它是在基因组测序工作之后形成的。确定特定基因组的序列是一个有限的、定义明确的问题。虽然每个基因都有一个序列，但每个基因产物并不具有“一个结构”，因为蛋白质通常具有多种功能状态，这些功能状态是由诸如翻译后修饰、配体结合诱导的构象变化、功能区域中结构的诱导等因素引起的，这些功能区域在蛋白质自身研究时显得无序，以及在一个以上的多蛋白复合物中发挥功能。因此，不能肯定《防扩散安全倡议》的基本目标是否可以实现，甚至是否明确界定。“工厂规模”科学是结构生物学的合适模型吗？就像DNA测序一样？即使可以从大多数开放阅读框架中获得3D结构，人们仍然需要问这些结构有多大价值。PSI产生蛋白质的结构，其功能和未来用途尚不清楚。结构本身很少提供来自结构，生物化学，细胞生物学和遗传学的综合方法的机械见解。如果功能信息不可用，则结构通常具有非常有限的实际意义。作为对这些批评和更大的结构生物学社区的普遍怀疑的回应，结构基因组学计划已经开始改变。出现了一些新的附带利益目标，特别是强调高通量技术开发的各个方面。
PSI Objectives The long-term objective of the NIGMS PSI is to obtain a complete description of protein fold space using the approach of structural genomics. As the term structural genomics implies, the PSI was conceived as a next step in the postgenomics era. However, the PSI is fundamentally different from the genome sequencing effort after which it is fashioned. Determining the sequence of a specific genome is a finite, well-defined problem. While it is clear that each gene has a sequence, each gene product does not have ‘‘a structure’’because proteins usually have multiple functional states resulting from factors such as posttranslational modifications, conformational changes induced by the binding of ligands, induction of structure in functional regions that appear disordered when the protein is studied on its own, and function in more than one multiprotein complex. Thus, it is not certain that the fundamental goal of the PSI is achievable or even well defined. Is ‘‘factory-scale’’science an appropriate model for structural biology as it is for DNA sequencing?Even if 3D structures could be obtained from most open reading frames, one still needs to ask how valuable these structures are. The PSI produces structures of proteins whose functions and future utility are not known. Structure, by itself, rarely provides the mechanistic insight that comes from a combined approach of structure, biochemistry, cell biology, and genetics. If functional information is not available, the structure will usually have very limited practical significance. Largely in response to such criticisms and the general skepticism of the greater structural biology community, structural genomics programs have begun to change. A number of new spin-off objectives have emerged, in particular putting emphasis on various aspects of technology development for high-throughput