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Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
Published on: July 14, 2015
Detecting compensatory covariation signals in protein evolution using reconstructed ancestral sequences.
K Fukami-Kobayashi1, D R Schreiber, S A Benner
1Center for Information Biology and DNA Data Bank of Japan, National Institute of Genetics, Mishima 411-8540, Japan.
Journal of Molecular Biology
|June 11, 2002
Summary
Charge compensatory covariation analysis on evolutionary trees reveals signals of protein evolution. This method, especially effective on ancestral sequences within secondary structures, aids in predicting protein structure and function.
Area of Science:
- Protein evolution
- Bioinformatics
- Structural biology
Background:
- Protein sequences evolve under functional constraints, sometimes involving charge-reversing amino acid replacements.
- Compensatory replacements, where two such changes restore protein function, can indicate proximity in folded protein structures.
- Identifying these compensatory pairs is crucial for understanding protein evolution and structure.
Purpose of the Study:
- To investigate the utility of charge compensatory covariation analysis in identifying protein evolutionary signals.
- To explore whether examining ancestral sequences on evolutionary trees enhances the detection of compensatory signals.
- To assess the potential of this method for secondary structure prediction and phylogenetic analysis.
Main Methods:
- Reconstructing ancestral protein sequences at nodes of phylogenetic trees.
- Analyzing charge compensatory covariation between amino acid positions along evolutionary branches.
- Comparing the signal strength when analyzing extant sequences versus ancestral sequences.
- Investigating the association between compensatory covariation and secondary structural elements.
Main Results:
- The charge compensatory signal is significantly more evident when analyzing ancestral sequences on evolutionary branches compared to extant sequences.
- The signal is particularly strong for position pairs within the same secondary structural unit (e.g., alpha-helix, beta-strand).
- Compensatory covariation analysis can aid in selecting the most parsimonious phylogenetic trees and assessing functional divergence.
Conclusions:
- Examining charge compensatory covariation on reconstructed evolutionary trees is a powerful tool for studying protein evolution.
- This approach offers novel insights into protein structure, function, and evolutionary history.
- The method has potential applications in secondary structure prediction and extracting biomedical information from proteomic databases.
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