Automated NMR resonance assignments and structure determination using a minimal set of 4D spectra
| Authors | |
|---|---|
| Year of publication | 2018 |
| Type | Article in Periodical |
| Magazine / Source | Nature Communications |
| MU Faculty or unit | |
| Citation | |
| web | https://www.nature.com/articles/s41467-017-02592-z.pdf |
| Doi | http://dx.doi.org/10.1038/s41467-017-02592-z |
| Keywords | PROTEIN-STRUCTURE DETERMINATION; CHEMICAL-SHIFTS; DIPOLAR COUPLINGS; NOESY ASSIGNMENT; LARGER PROTEINS; SPECTROSCOPY; ROSETTA; ROBUST; ALGORITHM; HOMOLOGY |
| Description | Automated methods for NMR structure determination of proteins are continuously becoming more robust. However, current methods addressing larger, more complex targets rely on analyzing 6-10 complementary spectra, suggesting the need for alternative approaches. Here, we describe 4D-CHAINS/autoNOE-Rosetta, a complete pipeline for NOE-driven structure determination of medium-to larger-sized proteins. The 4D-CHAINS algorithm analyzes two 4D spectra recorded using a single, fully protonated protein sample in an iterative ansatz where common NOEs between different spin systems supplement conventional through-bond connectivities to establish assignments of sidechain and backbone resonances at high levels of completeness and with a minimum error rate. The 4D-CHAINS assignments are then used to guide automated assignment of long-range NOEs and structure refinement in autoNOE-Rosetta. Our results on four targets ranging in size from 15.5 to 27.3 kDa illustrate that the structures of proteins can be determined accurately and in an unsupervised manner in a matter of days. |
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