Cavity scaling: Automated refinement of cavity-aware in protein function prediction

Brian Y. Chen, Drew H. Bryant, Viacheslav Y. Fofanov, David M. Kristensen, Amanda E. Cruess, Marek Kimmel, Olivier Lichtarge, Lydia E. Kavraki

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Algorithms for geometric and chemical comparison of protein substructure can be useful for many applications in protein function prediction. These motif matching algorithms identify matches of geometric and chemical similarity between well-studied functional sites, motifs, and substructures of functionally uncharacterized proteins, targets. For the purpose of function prediction, the accuracy of motif matching algorithms can be evaluated with the number of statistically significant matches to functionally related proteins, true positives (TPs), and the number of statistically insignificant matches to functionally unrelated proteins, false positives (FPs). Our earlier work developed cavity-aware motifs which use motif points to represent functionally significant atoms and C-spheres to represent functionally significant volumes. We observed that cavity-aware motifs match significantly fewer FPs than matches containing only motif points. We also observed that high-impact C-spheres, which significantly contribute to the reduction of FPs, can be isolated automatically with a technique we call Cavity Scaling. This paper extends our earlier work by demonstrating that C-spheres can be used to accelerate point-based geometric and chemical comparison algorithms, maintaining accuracy while reducing runtime. We also demonstrate that the placement of C-spheres can significantly affect the number of TPs and FPs identified by a cavity-aware motif. While the optimal placement of C-spheres remains a diffcult open problem, we compared two logical placement strategies to better understand C-sphere placement.

Original languageEnglish (US)
Pages (from-to)353-382
Number of pages30
JournalJournal of Bioinformatics and Computational Biology
Issue number2 A
StatePublished - Apr 2007
Externally publishedYes


  • Protein function
  • Protein structure
  • Refinement of protein motifs

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Computer Science Applications


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