High Accuracy Protein Structures from Minimal Sparse Paramagnetic Solid‐State NMR Restraints
High Accuracy Protein Structures from Minimal Sparse Paramagnetic Solid‐State NMR Restraints
复制标题
利用最小稀疏顺磁固态 NMR 约束获得高精度蛋白质结构
DOI：
10.1002/anie.201811895
复制
发表时间：
2019
期刊：
影响因子：
--
通讯作者：
MacCallum, Justin L.
中科院分区：
文献类型：
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作者：
Perez, Alberto;Gaalswyk, Kari;Jaroniec, Christopher P.;MacCallum, Justin L.
迫切需要新的计算工具来整合结构生物学中不同实验方法的数据。我们提出了一种将稀疏顺磁固体核磁共振约束与基于物理的原子模拟相结合的策略。我们的方法通过使用数据和通过广泛模拟校准的约束能量之间的半定量映射，明确地解释了实验数据的不确定性。我们将我们的方法应用于六个不同位置的Cu2+-EDTA标记的模型蛋白GB1的固体核磁共振数据。我们能够在图形处理器集群上在一天的计算时间内确定结构的精度为0.9 ä。我们进一步证明，在某些情况下，仅来自单个顺磁标签的数据就足以进行精确折叠。
There is a pressing need for new computational tools to integrate data from diverse experimental approaches in structural biology. We present a strategy that combines sparse paramagnetic solid‐state NMR restraints with physics‐based atomistic simulations. Our approach explicitly accounts for uncertainty in the interpretation of experimental data through the use of a semi‐quantitative mapping between the data and the restraint energy that is calibrated by extensive simulations. We apply our approach to solid‐state NMR data for the model protein GB1 labeled with Cu2+‐EDTA at six different sites. We are able to determine the structure to 0.9 Å accuracy within a single day of computation on a GPU cluster. We further show that in some cases, the data from only a single paramagnetic tag are sufficient for accurate folding.