title: Empirical correlation for the replacement of Ala by Gly: importance of amino acid secondary intrinsic propensities.
abstract: A series of Ala vs. Gly mutations at different helical and nonhelical positions of the chemotactic protein CheY, from E. coli, has been made. We have used this information to fit a general analytical equation that describes the free energy changes of an Ala to Gly mutation within +/- 0.45 kcal mol-1 with 95% confidence. The equation includes three terms: (1) the change in solvent-accessible hydrophobic surface area, corrected for the possible closure of the cavity left by deleting the C beta of the Ala; (2) the change in hydrophilic area of the nonintramolecularly hydrogen-bonded groups; and (3) the dihedral angles of the position being mutated. This last term extends the calculation to any conformation, not only alpha-helices. The general applicability of the equation for Ala vs. Gly mutations, when Ala or a small solvent-exposed polar residue is the wild-type residue, has been tested using data from other proteins: barnase, CI2 trypsin inhibitor, T4 lysozyme, and Staphylococcus nuclease. The predictive power of this simple approach offers the possibility of extending it to more complex mutations.
mesh_terms: D000409:Alanine / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D003198:Computer Simulation; D004926:Escherichia coli / Q000737:chemistry; D029968:Escherichia coli Proteins; D005998:Glycine / Q000737:chemistry*; D006860:Hydrogen Bonding; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics; D000072236:Methyl-Accepting Chemotaxis Proteins; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D000072236:Methyl-Accepting Chemotaxis Proteins; D011994:Recombinant Proteins; C000607606:cheY protein, E coli; D000409:Alanine; D005998:Glycine