Relationship Between Amino Acid Properties and Protein Stability: Buried Mutations |
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Authors: | M. Michael Gromiha Motohisa Oobatake Hidetoshi Kono Hatsuho Uedaira Akinori Sarai |
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Affiliation: | (1) Tsukuba Life Science Center, The Institute of Physical and Chemical Research (RIKEN), 3-1-1 Koyadai, Tsukuba, Ibaraki, 305-0074, Japan;(2) Present address: Faculty of Science and Technology, Meijo University, 1-501 Shiogamaguchi, Tenpaku-ku, Nagoya, 468-8502, Japan |
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Abstract: | In order to understand the mechanism of protein stability and to develop a simple method for predicting mutation-induced stability changes, we analyzed the relationship between stability changes caused by buried mutations and changes in 48 amino acid properties. As expected from the importance of hydrophobicity, properties reflecting hydrophobicity are strongly correlated with the stability of proteins. We found that subgroup classification based on secondary structure increased correlations significantly, and mutations within -strand segments correlated better than did those in -helical segments, which may result from stronger hydrophobicity of the -strands. Multiple regression analyses incorporating combinations of three properties from among all possible combinations of the 48 properties increased the correlation coefficient to 0.88 and by an average of 13% for all data sets. Analyzing the stability of tryptophan synthase mutants with Glu49 replaced by all other residues except Arg revealed that combining buriedness, solvent-accessible surface area for denatured protein, and unfolding Gibbs free energy change increased the correlation to 0.95. Consideration of sequence and structural information (neighboring residues in sequence and in space) did not significantly strengthen the correlations in buried mutations, suggesting that nonspecific interactions dominate in the interior of proteins. |
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Keywords: | Amino acid properties unfolding free energy change protein stability protein mutants multiple regression technique secondary and tertiary structures |
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