An iterative relaxation technique for the NMR backbone assignment problem

NMR spectroscopy is one of the popular experiments to determine protein structures. An important stage of protein structure determination by using NMR is protein backbone resonance assignment (or backbone assignment for short). Due to the messiness and disorder of NMR spectral data, backbone assignment is usually a tedious and time-consuming manual work. This raises a great interest in developing an efficient and automatic method to perform backbone assignment. An iterative algorithm is proposed that is equipped with two operations: grouping and linking. Grouping is responsible for peak picking and part of connectivity determination. Ideally, those peaks with the same H/sup N/ and N chemical shifts can be grouped together; peaks belonging to the same group can be used to determine the order of two consecutive spin systems. However, in real situation, grouping is a difficult task due to false positives and false negatives. We sometimes add hypothetic peaks to tackle false negatives and use linking operation to remove false positives. Linking is responsible for part of connectivity determination and backbone assignment. Given a protein sequence and partial connectivity information, we try to link connected spin systems as much as possible. False positive spin systems may create conflicts in the linking stage. To find a good assignment on a noisy dataset, the backbone assignment problem is modeled as a maximum independent set problem. Although the problem is NP-complete, there are heuristic methods that obtain pretty good results.