Metal binding sites in macromolecular structures

项目：大分子结构中的金属结合环境 摘要：金属离子在生物大分子的机理和结构中都起着至关重要的作用， 包括生化反应的催化、电子传递、气体结合和稳定 核苷酸和其他多聚磷酸化合物。然而，最近一项关于公开可用的结构的调查 在PDB中沉积的含有金属的蛋白质和核酸揭示了大量被错误识别的 和/或次优模拟的金属结合部位。这促使创建了一个诊断工具用于 金属结合微环境模型，“我的金属”(CMM)网络服务器 (http://csgid.org/csgid/metal_sites/)，检测金属结构中的几何和其他不规则性 结合位点并提醒研究人员注意金属分配中的潜在错误。作为三坐标测量机的生产版 已经得到了广泛的使用，研究界已经确定了未来发展的几个方向 主要兴趣：1)研究和验证大分子中不常见的重金属结合部位 结构；2)建立服务器，以提供定制的高质量、有效的金属结合部位的子集；3) 开发工具以自动检测电子密度中可能的金属结合位置，并识别和添加 结晶学模型建立和改进过程中最可能的金属离子；以及4)系统编目 金属结合结构和检测新的金属结合基序。我们建议开发的工具包，使用 作为基础的CMM包含几个模块，这些模块将独立工作或作为 结构建模、验证、解释和注释管道。这项提议不仅是为了 结构生物学家在晶体模型建立和验证过程中对新结构进行建模和验证 精致，但也适用于更广泛的受众-生物医学研究人员研究含有金属的蛋白质和 核酸。

Project: Metal binding environments in macromolecular structures Abstract: Metal ions play vital roles in both the mechanism and architecture of biological macromolecules, including the catalysis of biochemical reactions, electron transport, binding of gases, and stabilization of nucleotides and other polyphosphate compounds. However, a recent survey of publicly available structures of metal-containing proteins and nucleic acids deposited in the PDB revealed an abundance of misidentified and/or sub-optimally modeled metal binding sites. This prompted the creation of a diagnostic tool for the models of metal binding microenvironments, the "CheckMyMetal" (CMM) web server (http://csgid.org/csgid/metal_sites/), which detects geometric and other irregularities in structures of metal binding sites and alerts researchers to potential errors in metal assignment. As the production version of CMM has gained widespread usage, the research community has identified several directions for future development of major interest:1) investigate and validate uncommon heavy metal binding sites in macromolecular structures; 2) establish a server to provide customized subsets of high-quality, validated metal binding sites; 3) develop tools to automatically detect likely metal binding sites in electron density, and identify and add the most probable metal ion during crystallographic model building and refinement; and 4) systematically catalog metal binding architectures and detect new metal binding motifs. The toolkit we propose to develop, using CMM as a basis, contains several modules that will work either independently or as integrated steps in the structure modeling, validation, interpretation and annotation pipeline. This proposal was designed not only for structural biologists to model and validate new structures during crystallographic model building and refinement, but also for a broader audience—biomedical researchers studying metal-containing proteins and nucleic acids.