Role of structural and sequence information in the prediction of protein stability changes: comparison between buried and partially buried mutations.
Predicting mutation-induced changes in protein stability is one of the greatest challenges in molecular biology. In this work, we analyzed the correlation between stability changes caused by buried and partially buried mutations and changes in 48 physicochemical, energetic and conformational properties. We found that properties reflecting hydrophobicity strongly correlated with stability of buried mutations, and there was a direct relation between the property values and the number of carbon atoms. Classification of mutations based on their location within helix, strand, turn or coil segments improved the correlation of mutations with stability. Buried mutations within beta-strand segments correlated better than did those in alpha-helical segments, suggesting stronger hydrophobicity of the beta-strands. The stability changes caused by partially buried mutations in ordered structures (helix, strand and turn) correlated most strongly and were mainly governed by hydrophobicity. Due to the disordered nature of coils, the mechanism underlying their stability differed from that of the other secondary structures: the stability changes due to mutations within the coil were mainly influenced by the effects of entropy. Further classification of mutations within coils, based on their hydrogen-bond forming capability, led to much stronger correlations. Hydrophobicity was the major factor in determining the stability of buried mutations, whereas hydrogen bonds, other polar interactions and hydrophobic interactions were all important determinants of the stability of partially buried mutations. Information about local sequence and structural effects were more important for the prediction of stability changes caused by partially buried mutations than for buried mutations; they strengthened correlations by an average of 27% among all data sets.
Gromiha
M M
MM
Tsukuba Life Science Center, The Institute of Physical and Chemical Research (RIKEN), 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
Oobatake
M
M
Kono
H
H
Uedaira
H
H
Sarai
A
A
D000596:Amino Acids / Q000737:chemistry; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000235:genetics*; D012044:Regression Analysis
D000596:Amino Acids; D011506:Proteins