Assessing the utility of CASP14 models for molecular replacement.
Assessing the utility of CASP14 models for molecular replacement.
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作者：
Millán C;Keegan RM;Pereira J;Sammito MD;Simpkin AJ;McCoy AJ;Lupas AN;Hartmann MD;Rigden DJ;Read RJ
评估CASP模型在分子置换中的效用是衡量其在有价值的真实的世界应用中的使用。在CASP 7中，分子置换评估的指标涉及基于完全似然的分子置换检索;然而，这将可评估的靶标限制为在不对称单元中仅具有一个靶标拷贝的晶体结构，以及检索发现正确姿势的那些。在CASP 10中，使用LGA算法对叠加在靶点上的模型进行基于似然的刚体细化，以细化的对数似然增益（LLG）评分作为度量标准，取代了完整的分子置换搜索。这使得多拷贝目标和非常差的模型能够被评估，但仍然存在一个重要的问题：评估衍射数据的要求。我们在这里引入相对期望LLG（reLLG），它与衍射数据无关。该reLLG也独立于任何晶体形式，并且可以计算而不管目标的来源，无论是X射线，NMR还是cryo-EM。我们针对CASP 14中目标的LLG校准了reLLG，表明它是模型和组排名的稳健度量。与LLG一样，reLLG表明，准确的坐标误差估计为预测模型增加了大量价值。我们发现，CASP组的细化通常可以将不充分的初始模型转换为成功的MR搜索模型。与其他人的研究结果一致，我们表明AlphaFold 2模型足够好，并且可靠，可以超越其他当前用于尝试分子置换定相的模型生成策略。
The assessment of CASP models for utility in molecular replacement is a measure of their use in a valuable real‐world application. In CASP7, the metric for molecular replacement assessment involved full likelihood‐based molecular replacement searches; however, this restricted the assessable targets to crystal structures with only one copy of the target in the asymmetric unit, and to those where the search found the correct pose. In CASP10, full molecular replacement searches were replaced by likelihood‐based rigid‐body refinement of models superimposed on the target using the LGA algorithm, with the metric being the refined log‐likelihood‐gain (LLG) score. This enabled multi‐copy targets and very poor models to be evaluated, but a significant further issue remained: the requirement of diffraction data for assessment. We introduce here the relative‐expected‐LLG (reLLG), which is independent of diffraction data. This reLLG is also independent of any crystal form, and can be calculated regardless of the source of the target, be it X‐ray, NMR or cryo‐EM. We calibrate the reLLG against the LLG for targets in CASP14, showing that it is a robust measure of both model and group ranking. Like the LLG, the reLLG shows that accurate coordinate error estimates add substantial value to predicted models. We find that refinement by CASP groups can often convert an inadequate initial model into a successful MR search model. Consistent with findings from others, we show that the AlphaFold2 models are sufficiently good, and reliably so, to surpass other current model generation strategies for attempting molecular replacement phasing.
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影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
64.8
作者：
Harris CR;Millman KJ;van der Walt SJ;Gommers R;Virtanen P;Cournapeau D;Wieser E;Taylor J;Berg S;Smith NJ;Kern R;Picus M;Hoyer S;van Kerkwijk MH;Brett M;Haldane A;Del Río JF;Wiebe M;Peterson P;Gérard-Marchant P;Sheppard K;Reddy T;Weckesser W;Abbasi H;Gohlke C;Oliphant TE
通讯作者：
Oliphant TE
DOI：
10.1107/s2059798318004357
发表时间：
2018-04-01
期刊：
Acta crystallographica. Section D, Structural biology
影响因子：
--
作者：
Oeffner RD;Afonine PV;Millán C;Sammito M;Usón I;Read RJ;McCoy AJ
通讯作者：
McCoy AJ
影响因子：
5.7
作者：
Bunkoczi, Gabor;Wallner, Bjorn;Read, Randy J.
通讯作者：
Read, Randy J.
DOI：
10.1073/pnas.1701640114
发表时间：
2017-04-04
影响因子：
11.1
作者：
McCoy, Airlie J.;Oeffner, Robert D.;Read, Randy J.
通讯作者：
Read, Randy J.