Algorithms for structural comparison and statistical analysis of 3D protein motifs

Brian Y. Chen, Viacheslav Y. Fofanov, David M. Kristensen, Marek Kimmel, Olivier Lichtarge, Lydia E. Kavraki

Research output: Chapter in Book/Report/Conference proceedingConference contribution

29 Scopus citations


The comparison of structural subsites in proteins is increasingly relevant to the prediction of their biological function. To address this problem, we present the Match Augmentation algorithm (MA). Given a structural motif of interest, such as a functional site, MA searches a target protein structure for a match: the set of atoms with the greatest geometric and chemical similarity. MA is extremely efficient because it exploits the fact that the amino acids in a structural motif are not equally important to function. Using motif residues ranked on functional significance via the Evolutionary Trace (ET), MA prioritizes its search by initially forming matches with functionally significant residues, then, guided by ET, it augments this partial match stepwise until the whole motif is found. With this hierarchical strategy, MA runs considerably faster than other methods, and almost always identifies matches in homologs known to have cognate functional sites. Second, in order to interpret matches, we further introduce a statistical method using nonparametric density estimation of the frequency distribution of structural matches. Our results show that the hierarchy of functional importance within structural motifs speeds up the search within targets, and points to a new method to score their statistical significance.

Original languageEnglish (US)
Title of host publicationProceedings of the Pacific Symposium on Biocomputing 2005, PSB 2005
Number of pages12
StatePublished - 2005
Externally publishedYes
Event10th Pacific Symposium on Biocomputing, PSB 2005 - Big Island of Hawaii, United States
Duration: Jan 4 2005Jan 8 2005

Publication series

NameProceedings of the Pacific Symposium on Biocomputing 2005, PSB 2005


Conference10th Pacific Symposium on Biocomputing, PSB 2005
Country/TerritoryUnited States
CityBig Island of Hawaii

ASJC Scopus subject areas

  • Computational Theory and Mathematics
  • Biomedical Engineering


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