Development of computational methods for the rapid determination of NMR resonance assignment of large proteins

Abstract

In order to make the analysis process faster for large protein, we have developed a program for the automated assignment of backbone and 13CI? resonance of proteins with known primary sequence. Input to the program consists of cross-peak lists from triple TROSY NMR experiments, protein sequence and protein secondary structure information. A few algorithms are proposed to utilize a minimal number of 4D experiments, which well resolve the ambiguity of experiment data caused by heavy chemical shift degeneracy in large proteins. The combination method of both best-first deterministic algorithm and exhaustive search algorithm accomplishes nearly complete assignments in a short time, which agree with data of two previously studied proteins, a 67-kDa dimeric construct of p53 (279 residues) and Malate Synthase G (723 residues).