Improved molecular replacement by density- and energy-guided protein structure optimization.
Improved molecular replacement by density- and energy-guided protein structure optimization.
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DOI：
10.1038/nature09964
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发表时间：
2011-05-26
期刊：
影响因子：
64.8
通讯作者：
Baker, David
中科院分区：
文献类型：
--
作者：
DiMaio, Frank;Terwilliger, Thomas C.;Read, Randy J.;Wlodawer, Alexander;Oberdorfer, Gustav;Wagner, Ulrike;Valkov, Eugene;Alon, Assaf;Fass, Deborah;Axelrod, Herbert L.;Das, Debanu;Vorobiev, Sergey M.;Iwai, Hideo;Pokkuluri, P. Raj;Baker, David
蛋白质数据库中有超过60,000种蛋白质结构，通常可以使用其中一种结构来获得起始相信息并求解新的晶体结构。分子替代程序，即在晶体学单位细胞内寻找起始模型的位置，以最好地解释所测量的衍射振幅，然后是自动链示踪方法，已经允许快速解决大量蛋白质结构。尽管进行了大量的工作，但分子替换或随后的重建通常会失败，因为基于远端同源物且序列同源性低于30%的起始模型更加分散。在这里，我们表明，通过将蛋白质结构建模算法与用于晶体结构确定的算法相结合，可以大大减少这种限制。将Rosetta结构建模与Autobuild链追踪相结合的方法为13个x射线衍射数据集中的8个提供了高分辨率结构，这些数据集无法在专家晶体学家的实验室中解决，并且在应用了大量替代方法后仍未解决。我们估计，在现有方法失败的一半以上的情况下，新方法可以在没有实验相位信息的情况下快速确定结构，给定优于3.2Å分辨率的衍射数据集，不对称单元的4个或更少的拷贝，以及具有>20%序列同一性的同源蛋白结构的可用性。
With over 60,000 protein structures available in the Protein Data Bank, it is frequently possible use one of them to obtain starting phase information and to solve new crystal structures. Molecular replacement procedures, which search for placements of a starting model within the crystallographic unit cell that best account for the measured diffraction amplitudes, followed by automatic chain tracing methods, have allowed the rapid solution of large numbers of protein structures. Despite extensive work, molecular replacement or the subsequent rebuilding usually fail with more divergent starting models based on remote homologues with less than 30% sequence identity. Here we show that this limitation can be substantially reduced by combining algorithms for protein structure modeling with those developed for crystallographic structure determination. An approach integrating Rosetta structure modeling with Autobuild chain tracing yielded high-resolution structures for 8 of 13 X-ray diffraction datasets that could not be solved in the laboratories of expert crystallographers and that remained unsolved after application of an extensive array of alternative approaches. We estimate the new method should allow rapid structure determination without experimental phase information for over half the cases where current methods fail, given diffraction datasets of better than 3.2Å resolution, four or fewer copies in the asymmetric unit, and the availability of structures of homologous proteins with >20% sequence identity.
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DOI：
10.1107/s0108767386099622
发表时间：
1986-05-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION A
影响因子：
--
作者：
READ, RJ
通讯作者：
READ, RJ
影响因子：
48
作者：
Rodriguez, Dayte D.;Grosse, Christian;Uson, Isabel
通讯作者：
Uson, Isabel
DOI：
10.1107/s0907444904010145
发表时间：
2004-07-01
影响因子：
2.2
作者：
Schwarzenbacher, R;Godzik, A;Jaroszewski, L
通讯作者：
Jaroszewski, L
影响因子：
5.7
作者：
Schroeder, Gunnar F.;Brunger, Axel T.;Levitt, Michael
通讯作者：
Levitt, Michael
DOI：
10.1038/88640
发表时间：
2001-06-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Vitkup, D;Melamud, E;Sander, C
通讯作者：
Sander, C