6533b824fe1ef96bd12815d8

RESEARCH PRODUCT

A topology-constrained distance network algorithm for protein structure determination from NOESY data.

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description

This article formulates the multidi- mensional nuclear Overhauser effect spectroscopy (NOESY) interpretation problem using graph theory and presents a novel, bottom-up, topology-con- strained distance network analysis algorithm for NOESY cross peak interpretation using assigned resonances. AutoStructure is a software suite that implements this topology-constrained distance net- work analysis algorithm and iteratively generates structures using the three-dimensional (3D) protein structure calculation programs XPLOR/CNS or DY- ANA. The minimum input for AutoStructure in- cludes the amino acid sequence, a list of resonance assignments, and lists of 2D, 3D, and/or 4D-NOESY cross peaks. AutoStructure can also analyze ho- modimeric proteins when X-filtered NOESY experi- ments are available. The quality of input data and final 3D structures is evaluated using recall, preci- sion, and F-measure (RPF) scores, a statistical mea- sure of goodness of fit with the input data. AutoStruc- ture has been tested on three protein NMR data sets for which high-quality structures have previously been solved by an expert, and yields comparable high-quality distance constraint lists and 3D pro- tein structures in hours. We also compare several protein structures determined using AutoStructure with corresponding homologous proteins deter- mined with other independent methods. The pro- gram has been used in more than two dozen protein structure determinations, several of which have already been published. Proteins 2006;62:587- 603.