E. Lopezhernandez et L. Serrano, EMPIRICAL CORRELATION FOR THE REPLACEMENT OF ALA BY GLY - IMPORTANCE OF AMINO-ACID SECONDARY INTRINSIC PROPENSITIES, Proteins, 22(4), 1995, pp. 340-349
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.