Discarding Functional Residues from the Substitution Table Improves Predictions of Active Sites within Three-Dimensional Structures
2008

Improving Predictions of Protein Active Sites

Sample size: 81 publication 10 minutes Evidence: high

Author Information

Author(s): Gong Sungsam, Blundell Tom L., Levitt Michael

Primary Institution: University of Cambridge

Hypothesis

Discarding functional residues from substitution tables will enhance the prediction of active sites in proteins.

Conclusion

The new methodology significantly improves the prediction of active sites by increasing the Z-score and identifying more functional residues.

Supporting Evidence

  • The new ESSTs increased the Z-score by 98% at active site residues.
  • The methodology found 16% more active sites compared to the old ESST.
  • Discarding amino acids responsible for protein–protein interactions improved predictions.

Takeaway

This study shows that by ignoring certain important parts of proteins, we can better guess where the action happens in them.

Methodology

The study used the CRESCENDO program to test new Environment Specific Substitution Tables (ESSTs) that exclude functional residues.

Potential Biases

Potential bias from incomplete annotations of functional residues.

Limitations

The study may have high false positives and negatives due to the restricted definition of functional residues.

Statistical Information

P-Value

0.09

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pcbi.1000179

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