Direct use of unassigned resonances in NMR structure calculations with proxy residues
Direct use of unassigned resonances in NMR structure calculations with proxy residues
复制标题
DOI：
10.1021/ja058504q
复制
发表时间：
2006-06-14
影响因子：
15
通讯作者：
Bonvin, Alexandre M. J. J.
中科院分区：
文献类型：
--
作者：
Ab, Eiso;Pugh, David J. R.;Bonvin, Alexandre M. J. J.
我们提出了一种方法，显着提高（自动化）NMR结构测定的鲁棒性，允许NOE数据对应于未分配的NMR共振直接用于计算。未分配的共振由额外的原子或原子团表示，这些原子或原子团除了通过距离限制之外与常规蛋白质原子没有相互作用。这些所谓的“代理”残基可用于以与蛋白质的指定部分类似的方式产生基于NOE的距离限制。如果有足够的NOE信息可用，则预期约束将代理放置在接近未分配共振的正确原子的位置处，这可以促进随后的分配。通过提供关于未分配共振的可能身份的附加信息，可以进一步改善收敛。我们已经在广泛使用的自动分配和结构计算协议ARIA和CANDID中实现了这种方法。我们发现，它显着增加了结构计算的鲁棒性方面丢失的分配和产量的结构更高的质量。我们的方法仍然能够找到正确的折叠结构与高达30%的随机丢失的共振分配，甚至当只有骨干和β共振存在！这对基于NMR的结构蛋白质组学研究具有重要价值。
We present a method that significantly enhances the robustness of ( automated) NMR structure determination by allowing the NOE data corresponding to unassigned NMR resonances to be used directly in the calculations. The unassigned resonances are represented by additional atoms or groups of atoms that have no interaction with the regular protein atoms except through distance restraints. These so-called "proxy" residues can be used to generate NOE-based distance restraints in a similar fashion as for the assigned part of the protein. If sufficient NOE information is available, the restraints are expected to place the proxies at positions close to the correct atoms for the unassigned resonance, which can facilitate subsequent assignment. Convergence can be further improved by supplying additional information about the possible identities of the unassigned resonances. We have implemented this approach in the widely used automated assignment and structure calculation protocols ARIA and CANDID. We find that it significantly increases the robustness of structure calculations with regard to missing assignments and yields structures of higher quality. Our approach is still able to find correctly folded structures with up to 30% randomly missing resonance assignments, and even when only backbone and beta resonances are present! This should be of significant value to NMR-based structural proteomics initiatives.