Integrated NMR for Complex Systems

TR&D 3 SUMMARY Assigning each resonance in an NMR spectrum to individual atoms in a molecule is essential to almost every NMR project. Automated programs are successful for assignment of smaller soluble proteins, but frequently fail for larger proteins and complexes, asymmetric oligomers, and systems with predominantly one secondary

structure such as helical membrane proteins or beta-sheet fibrils. For most systems, the assignment process – sample preparation, experiment selection, data processing, signal identification and data analysis to achieve assignments – is expensive, time consuming and requires significant manual effort. This manual intervention

requires expertise to be done well, and poor execution at any step makes subsequent steps more difficult. Here we propose to develop algorithms and guided user interfaces that will automate processing of higher dimensional spectra, improve automated peak picking, and tailor acquisition of NMR spectra for assignment to

maximize data and minimize cost in a fully-automated, integrated data acquisition, assignment and structure determination platform. Automation of this process will improve the reproducibility of NMR data analysis, reduce the time and cost of NMR studies, and make NMR more accessible to the broad research community.