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Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
Published on: July 14, 2015
Structural and functional roles of coevolved sites in proteins
Saikat Chakrabarti1, Anna R Panchenko
1National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, United States of America. chakraba@ncbi.nlm.nih.gov
Plos One
|January 13, 2010
Summary
Residue coevolution in proteins helps maintain structure and function. Functionally important sites often coevolve, with charge compensatory substitutions preserving salt bridges.
Area of Science:
- Biochemistry
- Structural Biology
- Computational Biology
Background:
- Understanding residue covariations is crucial for protein engineering.
- Coevolution maintains protein structural-functional integrity during functional modifications.
- Debate exists regarding coevolved residue locations, signal strength, and role in functional diversification.
Purpose of the Study:
- Investigate the scale and nature of residue coevolution in protein structure-function.
- Analyze the spatial distribution and functional importance of coevolved residues.
Main Methods:
- Large-scale study of residue coevolutionary networks.
- Analysis of network properties (clustering coefficient, shortest path lengths).
- Examination of coevolved sites' functional importance (active sites, binding sites) and spatial proximity.
Main Results:
- Coevolutionary networks exhibit 'small-world' characteristics.
- 11% of functionally important sites are coevolved.
- Active sites (15%) coevolve more frequently than protein (11%) or ligand (9%) binding sites.
- Coevolved sites are often spatially proximate, with 80% of charge compensatory substitutions within 5Å.
Conclusions:
- A significant fraction of functionally important sites undergo coevolution.
- Compensatory substitutions in spatially proximal sites likely drive coevolutionary mechanisms.
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