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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 determinants of protein evolution are context-sensitive at the residue level
1Boston University, Boston, USA.
Molecular Biology and Evolution
|July 15, 2009
Summary
Protein residue evolution is strongly linked to structural properties like solvent exposure and burial depth. These continuous properties, not just surface vs. buried distinctions, quantitatively impact evolutionary rates and protein-protein interactions.
Area of Science:
- Structural biology
- Evolutionary biology
- Computational biology
Background:
- Protein residue microenvironment properties influence selective constraint.
- Structure-based protein evolution studies often use simplified residue classifications (surface/buried, interfacial/non-interfacial).
Purpose of the Study:
- To explore relationships between residue evolution and continuous structural properties.
- To investigate how global protein context affects structure-evolution relationships.
- To analyze selective constraint at protein-protein interfaces.
Main Methods:
- Utilized homology-mapped yeast protein structures.
- Analyzed continuous structural properties: solvent accessibility, contact density/distribution, burial depth.
- Quantified evolutionary rate using d(N)/d(S) ratios.
Main Results:
- Confirmed solvent exposure as a major determinant of residue evolution, showing a strong, positive, linear relationship with evolutionary rate (d(N)/d(S)).
- Identified a weaker secondary effect of packing density.
- Demonstrated that increasing protein-core size accelerates constraint relaxation with solvent exposure.
- Revealed two components of interface constraint: continuous structural constraint and fixed functional constraint.
Conclusions:
- Residue burial is a continuous property with quantitative fitness implications.
- Structure-evolution relationships vary systematically with global protein context.
- Protein-protein interfaces exhibit both continuous structural and fixed functional constraints.
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