EMPIRICAL CORRELATION FOR THE REPLACEMENT OF ALA BY GLY - IMPORTANCE OF AMINO-ACID SECONDARY INTRINSIC PROPENSITIES

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 t hat 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 Cp of the Ala; (2) the change in hydrophilic area of the nonintramole cularly hydrogen-bonded groups; and (3) the dihedral angles of the pos ition being mutated. This last term extends the calculation to any con formation, not only or-helices. The general applicability of the equat ion for Ala vs. Gly mutations, when Ala or a small solvent-exposed pol ar residue is the wild-type residue, has been tested using data from o ther proteins: barnase, CI2 trypsin inhibitor, T4 lysozyme, and Staphy lococcus nuclease. The predictive power of this simple approach offers the possibility of extending it to more complex mutations. (C) 1995 W iley-Liss, Inc.