分子置换中经过处理的预测模型的成功率:对 AlphaFold 时代实验分期的影响。

IF 2.6 4区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS
Ronan M Keegan, Adam J Simpkin, Daniel J Rigden
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引用次数: 0

摘要

AlphaFold2(AF2)和类似工具提供的高精度蛋白质结构预测极大地扩展了分子置换(MR)在晶体结构求解中的应用。许多结构可以使用原始模型、经过处理以去除不可靠部分的结构或拆分成不同结构单元的模型进行常规求解。因此,有多少结构和哪些结构仍然需要使用单波长反常衍射(SAD)等实验相位分析方法是一个未决问题。在此,我们使用大量通过 SAD 解决的 PDB 沉积物来解决这一问题。其中绝大多数(87%)可以使用未经编辑或编辑极少的 AF2 预测来求解。另外 18 个(4%)在使用 Slice'N'Dice 对 AF2 预测进行拆分后,直接产生了 MR,尽管不同的拆分方法成功的案例集略有不同。研究还发现,更多的独特目标可以通过其他建模方法(如 ESMFold,4 个案例)、其他 MR 方法(如 ARCIMBOLDO 和 AMPLE,各 2 个案例)以及使用 AlphaFold-Multimer 或 UniFold 建立多聚物模型(3 个案例)来解决。最终,只有 12 个案例(占 SAD 相位集的 3%)没有通过本文测试的任何形式的 MR,这对实验相位对于大分子结构求解仍然至关重要的案例数量和特征提供了宝贵的提示。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The success rate of processed predicted models in molecular replacement: implications for experimental phasing in the AlphaFold era.

The availability of highly accurate protein structure predictions from AlphaFold2 (AF2) and similar tools has hugely expanded the applicability of molecular replacement (MR) for crystal structure solution. Many structures can be solved routinely using raw models, structures processed to remove unreliable parts or models split into distinct structural units. There is therefore an open question around how many and which cases still require experimental phasing methods such as single-wavelength anomalous diffraction (SAD). Here, this question is addressed using a large set of PDB depositions that were solved by SAD. A large majority (87%) could be solved using unedited or minimally edited AF2 predictions. A further 18 (4%) yield straightforwardly to MR after splitting of the AF2 prediction using Slice'N'Dice, although different splitting methods succeeded on slightly different sets of cases. It is also found that further unique targets can be solved by alternative modelling approaches such as ESMFold (four cases), alternative MR approaches such as ARCIMBOLDO and AMPLE (two cases each), and multimeric model building with AlphaFold-Multimer or UniFold (three cases). Ultimately, only 12 cases, or 3% of the SAD-phased set, did not yield to any form of MR tested here, offering valuable hints as to the number and the characteristics of cases where experimental phasing remains essential for macromolecular structure solution.

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来源期刊
Acta Crystallographica. Section D, Structural Biology
Acta Crystallographica. Section D, Structural Biology BIOCHEMICAL RESEARCH METHODSBIOCHEMISTRY &-BIOCHEMISTRY & MOLECULAR BIOLOGY
CiteScore
4.50
自引率
13.60%
发文量
216
期刊介绍: Acta Crystallographica Section D welcomes the submission of articles covering any aspect of structural biology, with a particular emphasis on the structures of biological macromolecules or the methods used to determine them. Reports on new structures of biological importance may address the smallest macromolecules to the largest complex molecular machines. These structures may have been determined using any structural biology technique including crystallography, NMR, cryoEM and/or other techniques. The key criterion is that such articles must present significant new insights into biological, chemical or medical sciences. The inclusion of complementary data that support the conclusions drawn from the structural studies (such as binding studies, mass spectrometry, enzyme assays, or analysis of mutants or other modified forms of biological macromolecule) is encouraged. Methods articles may include new approaches to any aspect of biological structure determination or structure analysis but will only be accepted where they focus on new methods that are demonstrated to be of general applicability and importance to structural biology. Articles describing particularly difficult problems in structural biology are also welcomed, if the analysis would provide useful insights to others facing similar problems.
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