title: Contribution of the hydrophobic effect to globular protein stability.
abstract: The decrease in conformational stability, delta(delta G), has been measured for 72 aliphatic side-chain mutants from four proteins in which a larger side-chain is replaced by a smaller side-chain so that steric effects are minimal. When these delta(delta G) values are corrected to the same accessibility, namely 100% buried, then the following -delta(delta G) values per -CH2- group (in kcal/mol) are obtained: Ile----Val (1.26), Ala (1.26), Gly (1.26); Leu----Ala (1.16), Gly (1.21); Val----Ala (1.23), Gly (1.53). The average of these values is 1.27(+/- 0.07) kcal/mol. The 72 individual values range from 0 to 2.4 kcal/mol with an average value of 1.27(+/- 0.51) (standard deviation) kcal/mol. When the delta Gtr values from n-octanol to water are corrected for the difference in volume between the solutes and the solvents, the average value for the same substitutions is 1.25(+/- 0.05) kcal/mol. This suggests that proteins gain 1.3(+/- 0.5) kcal/mol in stability for each -CH2- group buried in folding, and, furthermore, that the volume corrected delta Gtr values for n-octanol for the amino acid side-chains provide good estimates of the contribution of the hydrophobic effect to globular protein stability.
authors.affiliation: Department of Medical Biochemistry and Genetics, Texas A&M University, College Station 77843-1114.
authors.forename: C N
authors.initials: CN
authors.lastname: Pace
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D001426:Bacterial Proteins; D004252:DNA Mutational Analysis; D008836:Micrococcal Nuclease / Q000737:chemistry*; D009113:Muramidase / Q000737:chemistry*; D011487:Protein Conformation; D012260:Ribonucleases / Q000737:chemistry*; D014764:Viral Proteins / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D001426:Bacterial Proteins; D014764:Viral Proteins; C068293:gene 5 protein, Enterobacteria phage T4; D012260:Ribonucleases; C019760:Bacillus amyloliquefaciens ribonuclease; D008836:Micrococcal Nuclease; D009113:Muramidase