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Revisiting "reverse hydrophobic effect": applicable only to coil mutations at the surface
1Computational Biology Research Center (CBRC), National Institute of Advanced Industrial Science and Technology (AIST), AIST Tokyo Waterfront Bio-IT Research Building, 2-42 Aomi, Koto-ku, Tokyo 135-0064, Japan. michael-gromiha@aist.go.jp
Biopolymers
|March 14, 2009
Summary
Protein mutations affecting hydrophobicity can alter protein stability. This study confirms a reverse correlation between hydrophobicity and stability for exposed coil mutations and explores relationships in other mutant types.
Area of Science:
- Biochemistry
- Structural Biology
- Protein Engineering
Background:
- The relationship between amino acid hydrophobicity and protein stability is complex.
- Previous work suggested an inverse correlation between increased hydrophobicity and protein stability.
Purpose of the Study:
- To investigate the relationship between amino acid substitution, hydrophobicity, and protein stability across various structural contexts.
- To analyze how secondary structure and solvent accessibility influence these relationships.
Main Methods:
- Analysis of mutant proteins with substitutions at different locations.
- Categorization of mutants based on secondary structure (coil, helix, strand) and solvent accessibility (exposed, partially buried, buried).
- Correlation analysis of stability changes with hydrophobicity, entropy, and flexibility.
Main Results:
- Confirmed a reverse correlation between hydrophobicity and stability for exposed coil mutations, with one exception.
- Observed this reverse correlation in partially buried coil mutants.
- Found that stability of exposed helical mutants depends on conformational properties.
- Identified direct relationships between hydrophobicity and stability for buried/partially buried helical and strand mutants, contrasting with entropy and flexibility.
- Highlighted the importance of surrounding residues in determining stability changes.
Conclusions:
- The relationship between hydrophobicity and protein stability is context-dependent, varying with secondary structure and solvent accessibility.
- Surrounding residues play a critical role in modulating the impact of mutations on protein stability.
- These findings offer insights into the general principles governing protein stability upon amino acid substitution.
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