Automated NMR resonance assignments and structure determination using a minimal set of 4D spectra
Year: 2018
Type: article
Abstract: 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.
Source: Nature Communications
Language: English
Subfield: Spectroscopy
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: G2061982546, G2099282922, 800 MHz NMR Spectrometer and Helium Cryoprobe, G2693309452, G3033345171, G3496015395, Molecular architecture of protein-DNA complexes involved in Nucleotide Excision Repair, Structural studies of Nucleotide Excision Repair for drug development targeting protein-DNA interactions, CEITEC 2020, G6203945784, G6231564467, G9000154247, G9000262362
OpenAlex ID: W2786573727