The challenge of protein structure determination—lessons from structural genomics

The process of experimental determination of protein structure is marred with a high ratio of failures at many stages. With availability of large quantities of data from high‐throughput structure determination in structural genomics centers, we can now learn to recognize protein features correlated...

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Bibliographic Details
Published in:Protein science 2007-11, Vol.16 (11), p.2472-2482
Main Authors: Slabinski, Lukasz, Jaroszewski, Lukasz, Rodrigues, Ana P.C., Rychlewski, Leszek, Wilson, Ian A., Lesley, Scott A., Godzik, Adam
Format: Article
Language:English
Subjects:
Computational Biology - methods
Crystallization
Crystallography, X-Ray - methods
Databases, Protein
Genomics - methods
Isoelectric Focusing
Magnetic Resonance Spectroscopy - methods
Probability
Protein Conformation
protein crystallization
protein structure initiative
Protein Structure, Secondary
Proteins - chemistry
Proteomics - methods
Sequence Analysis, Protein
structural genomics
target selection
X‐ray crystallography
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Summary:The process of experimental determination of protein structure is marred with a high ratio of failures at many stages. With availability of large quantities of data from high‐throughput structure determination in structural genomics centers, we can now learn to recognize protein features correlated with failures; thus, we can recognize proteins more likely to succeed and eventually learn how to modify those that are less likely to succeed. Here, we identify several protein features that correlate strongly with successful protein production and crystallization and combine them into a single score that assesses “crystallization feasibility.” The formula derived here was tested with a jackknife procedure and validated on independent benchmark sets. The “crystallization feasibility” score described here is being applied to target selection in the Joint Center for Structural Genomics, and is now contributing to increasing the success rate, lowering the costs, and shortening the time for protein structure determination. Analyses of PDB depositions suggest that very similar features also play a role in non‐high‐throughput structure determination, suggesting that this crystallization feasibility score would also be of significant interest to structural biology, as well as to molecular and biochemistry laboratories.
ISSN:0961-8368
1469-896X
DOI:10.1110/ps.073037907