| Abstract
| - NMR spectroscopy and X-ray crystallography, the two primary experimental methods for proteinstructure determination at high resolution, have different advantages and disadvantages in terms of samplepreparation and data collection and analysis. It is therefore of interest to assess their complementaritywhen applied to small proteins. Structural genomics/proteomics projects provide an ideal opportunity tomake such comparisons as they generate data in a systematic manner for large enough numbers of proteinsto allow firm conclusions to be drawn. Here we report a comparison for 263 unique proteins screened byboth NMR spectroscopy and X-ray crystallography in our structural proteomics pipeline. Only 21 targets(8%) were deemed amenable to both methods based on an initial 2D 15N-HSQC NMR spectrum andoptimized crystallization trials. However, the use of both methods in the pipeline increased the total numberof targets amenable to structure determination to 107, with 43 amenable to NMR only and 43 amenable toX-ray crystallographic methods only. We did not observe a correlation between 15N-HSQC spectral qualityand the success of the same protein in crystallization screens. Similar results were found for an independentset of 159 proteins as reported in the accompanying paper by Snyder et al. Thus, we conclude that bothmethods are highly complementary, and in order to increase the number of proteins suited for structuredetermination, we suggest that both methods be used in parallel in screening of all small proteins for structuredetermination.
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