title: An expectation/maximization nuclear vector replacement algorithm for automated NMR resonance assignments.
abstract: We report an automated procedure for high-throughput NMR resonance assignment for a protein of known structure, or of an homologous structure. Our algorithm performs Nuclear Vector Replacement (NVR) by Expectation/Maximization (EM) to compute assignments. NVR correlates experimentally-measured NH residual dipolar couplings (RDCs) and chemical shifts to a given a priori whole-protein 3D structural model. The algorithm requires only uniform (15)N-labelling of the protein, and processes unassigned H(N)-(15)N HSQC spectra, H(N)-(15)N RDCs, and sparse H(N)-H(N) NOE's (d(NN)s). NVR runs in minutes and efficiently assigns the (H(N),(15)N) backbone resonances as well as the sparse d(NN)s from the 3D (15)N-NOESY spectrum, in O (n(3)) time. The algorithm is demonstrated on NMR data from a 76-residue protein, human ubiquitin, matched to four structures, including one mutant (homolog), determined either by X-ray crystallography or by different NMR experiments (without RDCs). NVR achieves an average assignment accuracy of over 99%. We further demonstrate the feasibility of our algorithm for different and larger proteins, using different combinations of real and simulated NMR data for hen lysozyme (129 residues) and streptococcal protein G (56 residues), matched to a variety of 3D structural models.
authors.affiliation: Dartmouth Computer Science Department, Hanover, NH 03755, USA.
authors.forename: Christopher James
authors.initials: CJ
authors.lastname: Langmead
authors.forename: Bruce Randall
authors.initials: BR
authors.lastname: Donald
mesh_terms: D000465:Algorithms; D000818:Animals; D002247:Carbon Isotopes / Q000737:chemistry; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D015394:Molecular Structure; D009113:Muramidase / Q000737:chemistry; D009587:Nitrogen Isotopes / Q000737:chemistry; D025801:Ubiquitin / Q000737:chemistry
chemical_list: D002247:Carbon Isotopes; D009587:Nitrogen Isotopes; D025801:Ubiquitin; D009113:Muramidase