title: Revisiting "reverse hydrophobic effect": applicable only to coil mutations at the surface.
abstract: In a seminal paper, Pakula and Sauer (Nature, 1990, 344, 363-364) demonstrated that the increase in side-chain hydrophobicity has a reverse relationship with protein stability. We have addressed this problem with several examples of mutants that span at different locations in protein structure based on secondary structure and solvent accessibility. We confirmed that the stability change upon single coil mutation at exposed region is reversely correlated with hydrophobicity with a single exception. In addition, we found the existence of such relationship in partially buried coil mutants. The stability of exposed helical mutants is governed by conformational properties. In buried and partially buried helical and strand mutants properties reflecting hydrophobicity have direct relationship with stability, whereas an opposite relationship was obtained with entropy and flexibility. The structural analysis of partially buried/exposed mutants showed that the surrounding residues are important for the stability change upon mutation. These results provide insights to understand the general behavior for the stability of proteins upon amino acid substitutions.
authors.affiliation: Computational 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
authors.forename: M Michael
authors.initials: MM
authors.lastname: Gromiha
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008969:Molecular Sequence Data; D009113:Muramidase / Q000737:chemistry / Q000235:genetics; D050505:Mutant Proteins / Q000737:chemistry; D009154:Mutation / Q000235:genetics*; D017510:Protein Folding; D055550:Protein Stability; D017433:Protein Structure, Secondary; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D050505:Mutant Proteins; D009113:Muramidase