Core F: Structure

虽然非洲联盟的基础设施和组织受到《防扩散安全倡议》的启发，但它们的目标有很大的不同，这为非洲联盟提供了独特的机会。历史上，PSI的主要焦点一直是增加折叠和序列空间的结构覆盖，并且特定序列家族的任何成员的结构都是整个家族的合适代表。因此，所有防扩散安全倡议的目标都是 进行广泛的分类，并且只有那些在流水线的每一步表现出高度有利特征的序列才被用于结构确定。这种方法使折叠/序列覆盖最大化，而不管功能重要性如何。与此相反，基因组学明确地关注功能的发现，因此将经常需要研究基因组学序列，需要付出超过这些的努力。 通常用于任何单独的PSI目标。因此，PC和SC被定位为在蛋白质纯化、结晶、数据收集和结构确定中实施相当多的初级和次级拯救策略，以便成功地起诉那些在功能、机制和进化方面信息最丰富的靶标。特别是，如下文所述， SC准备在结晶、数据收集和结构测定方面提供广泛和扩展的努力。此外，除了结构发现管道的这些传统方面，SC将投入大量资源用于配体鉴定工作，以1）获得直接的功能见解，2）帮助结晶，3）最大限度地利用结构进行计算配体发现。

While the infrastructure and organization of the EFI are inspired by the PSI, there are significant differences in their objectives, which offer unique opportunities for the EFI. Historically, the primary focus of the PSI has been on increasing the structural coverage of fold and sequence space, and the structure of any member of a particular sequence family is a suitable representative of the entire family. Consequently, all PSI targets are subjected to extensive triage, and only those sequences exhibiting highly favorable characteristics at each step of the pipeline are taken fonward for structure determination. This approach maximizes fold/sequence coverage regardless of functional importance. In contrast, the EFI is explicitly concerned with the discovery of function and thus will frequently necessitate the study of recalcitrant sequences requiring efforts that exceed those commonly expended on any individual PSI target. Accordingly, the PC and SC are positioned to implement considerable primary and secondary rescue strategies in protein purification, crystallization, data collection and structure determination in order to successfully prosecute those targets that are most informative in terms of function, mechanism and evolution. In particular, as needed and detailed below, the expert technical staff of the SC is prepared to provide extensive and expanded efforts in crystallization, data collection and structure determination. Furthermore, beyond these traditional aspects of the structure discovery pipeline, the SC will devote considerable resources to ligand identification efforts in order to 1) obtain direct functional insights, 2) aid in crystallization, and 3) maximize the utility of structures for computational ligand discovery.