Ab initio solution of macromolecular crystal structures without direct methods
Ab initio solution of macromolecular crystal structures without direct methods
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DOI：
10.1073/pnas.1701640114
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发表时间：
2017-04-04
影响因子：
11.1
通讯作者：
Read, Randy J.
中科院分区：
文献类型：
--
作者：
McCoy, Airlie J.;Oeffner, Robert D.;Read, Randy J.
大多数大分子的晶体结构是使用分子置换的方法来确定的，在该方法中，已知的相关结构被旋转和平移以提供新结构的初始原子模型。在基于似然性的分子置换搜索的信噪比的理论理解已经发展到占模型的质量和完整性的影响，以及衍射数据的分辨率。在这里，我们表明，与目前的信念，分子置换不需要被限制到使用的模型，包括一个相当大的一部分的未知结构。相反，基于可能性的方法允许连续的应用程序，这取决于模型的质量和数据的分辨率。出乎意料的是，我们对分子置换中的信噪比的理解导致了这样的发现，即在足够高分辨率的数据下，通常在蛋白质中发现的元素的单个原子那么小的片段可以产生大分子结构的从头算解决方案，包括一些逃避传统直接方法的解决方案。
The majority of macromolecular crystal structures are determined using the method of molecular replacement, in which known related structures are rotated and translated to provide an initial atomic model for the new structure. A theoretical understanding of the signal-to-noise ratio in likelihood-based molecular replacement searches has been developed to account for the influence of model quality and completeness, as well as the resolution of the diffraction data. Here we show that, contrary to current belief, molecular replacement need not be restricted to the use of models comprising a substantial fraction of the unknown structure. Instead, likelihood-based methods allow a continuum of applications depending predictably on the quality of the model and the resolution of the data. Unexpectedly, our understanding of the signal-to-noise ratio in molecular replacement leads to the finding that, with data to sufficiently high resolution, fragments as small as single atoms of elements usually found in proteins can yield ab initio solutions of macromolecular structures, including some that elude traditional direct methods.