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Large-scale co-evolution analysis of protein structural interlogues using the global protein structural interactome
Wan K Kim1, Dan M Bolser, Jong H Park
1MRC Rosalind Franklin Centre for Genome Research, Hinxton, Cambridge CB10 1SB, UK.
Bioinformatics (Oxford, England)
|February 7, 2004
Summary
Protein families co-evolve, maintaining structural and functional links. Analyzing over 900 pairs in the protein structural interactome map (PSIMAP) revealed significant co-evolutionary patterns, enhancing interaction prediction accuracy.
Area of Science:
- Structural biology
- Bioinformatics
- Evolutionary biology
Background:
- Protein-protein interactions require co-evolution for functional and structural complementarity.
- Phylogenetic tree similarity reflects co-evolutionary trends in interacting protein families.
- Previous studies on co-evolution were not systematically conducted across a broad scope.
Purpose of the Study:
- To systematically investigate the degree of protein family co-evolution.
- To analyze co-evolution across a global protein structural interactome map (PSIMAP).
- To assess the utility of co-evolution analysis in predicting protein interactions.
Main Methods:
- Analysis of over 900 protein family pairs.
- Utilized the protein structural interactome map (PSIMAP) database.
- Examined co-evolutionary patterns in both intra-molecular and inter-molecular protein interactions.
Main Results:
- Significant co-evolutionary correlation found in 45% of SCOPs Family level pairs, increasing to 78% for reliable interactions.
- Intra-molecular interactions exhibited stronger co-evolution than inter-molecular interactions, though patterns were fundamentally similar.
- Co-evolution analysis improved prediction accuracy, yielding a nearly 5-fold enrichment of true interactions with 79.2% sensitivity and 78.6% specificity.
Conclusions:
- Co-evolutionary analysis is a valid method for enhancing protein interaction prediction accuracy.
- The findings support the use of co-evolution in conjunction with predictive tools like PSIMAP.
- Co-evolutionary signals are present in both intra- and inter-molecular protein interactions, with distinct patterns when different interfaces are involved.