Prediction of functional specificity determinants from protein sequences using log-likelihood ratios

Jimin Pei, Wei Cai, Lisa N. Kinch, Nick V. Grishin

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


Motivation: A number of methods have been developed to predict functional specificity determinants in protein families based on sequence information. Most of these methods rely on pre-defined functional subgroups. Manual subgroup definition is difficult because of the limited number of experimentally characterized subfamilies with differing specificity, while automatic subgroup partitioning using computational tools is a non-trivial task and does not always yield ideal results. Results: We propose a new approach SPEL (specificity positions by evolutionary likelihood) to detect positions that are likely to be functional specificity determinants. SPEL, which does not require subgroup definition, takes a multiple sequence alignment of a protein family as the only input, and assigns a P-value to every position in the alignment. Positions with low P-values are likely to be important for functional specificity. An evolutionary tree is reconstructed during the calculation, and P-value estimation is based on a random model that involves evolutionary simulations. Evolutionary log-likelihood is chosen as a measure of amino acid distribution at a position. To illustrate the performance of the method, we carried out a detailed analysis of two protein families (LacI/PurR and G protein α subunit), and compared our method with two existing methods (evolutionary trace and mutual information based). All three methods were also compared on a set of protein families with known ligand-bound structures.

Original languageEnglish (US)
Pages (from-to)164-171
Number of pages8
Issue number2
StatePublished - Jan 15 2006

ASJC Scopus subject areas

  • Statistics and Probability
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Computational Theory and Mathematics
  • Computational Mathematics


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