Techniques, tools and best practices for ligand electron-density analysis and results from their application to deposited crystal structures
Techniques, tools and best practices for ligand electron-density analysis and results from their application to deposited crystal structures
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DOI：
10.1107/s0907444912044423
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发表时间：
2013-02-01
影响因子：
2.2
通讯作者：
Rupp, Bernhard
中科院分区：
文献类型：
--
作者：
Pozharski, Edwin;Weichenberger, Christian X.;Rupp, Bernhard
由于仪器自动化程度的提高和软件的不断改进，越来越多的生物分子的晶体学研究由非专家进行。虽然改进的验证几乎可以确保结构模型中蛋白质部分的重大错误非常罕见，但在配体-蛋白质复合物结构中，通常科学家最感兴趣的是，模糊的配体电子密度通常难以解释，并且建模的配体通常更难以正确验证。在这里，（i）主要的技术原因和潜在的人为因素导致的配体结构模型中的问题;（ii）最常见的类别的建设错误或过度解释进行了分类;（iii）一些指导性和具体的例子进行了详细讨论，包括电子密度为基础的分析不包含任何配体的配体结构;（iv）建议避免此类错误的方法，并讨论了对数据库有效性的影响，以及（v）提供了一种用户友好的软件工具，允许非专家用户方便地检查配体密度。
As a result of substantial instrumental automation and the continuing improvement of software, crystallographic studies of biomolecules are conducted by non-experts in increasing numbers. While improved validation almost ensures that major mistakes in the protein part of structure models are exceedingly rare, in ligand-protein complex structures, which in general are most interesting to the scientist, ambiguous ligand electron density is often difficult to interpret and the modelled ligands are generally more difficult to properly validate. Here, (i) the primary technical reasons and potential human factors leading to problems in ligand structure models are presented; (ii) the most common categories of building errors or overinterpretation are classified; (iii) a few instructive and specific examples are discussed in detail, including an electron-density-based analysis of ligand structures that do not contain any ligands; (iv) means of avoiding such mistakes are suggested and the implications for database validity are discussed and (v) a user-friendly software tool that allows non-expert users to conveniently inspect ligand density is provided.