Surveys of protein crystal structures have revealed
that amino acids show unique structural preferences for
the N1, N2, and N3 positions in the first turn of the α-helix.
We have therefore extended helix-coil theory to include
statistical weights for these locations. The helix content
of a peptide in this model is a function of N-cap, C-cap,
N1, N2, N3, C1, and helix interior (N4 to C2) preferences.
The partition function for the system is calculated using
a matrix incorporating the weights of the fourth residue
in a hexamer of amino acids and is implemented using a
FORTRAN program. We have applied the model to calculate
the N1 preferences of Gln, Val, Ile, Ala, Met, Pro, Leu,
Thr, Gly, Ser, and Asn, using our previous data on helix
contents of peptides Ac-XAKAAAAKAAGY-CONH2.
We find that Ala has the highest preference for the N1
position. Asn is the most unfavorable, destabilizing a
helix at N1 by at least 1.4 kcal mol−1
compared to Ala. The remaining amino acids all have similar
preferences, 0.5 kcal mol−1 less than
Ala. Gln, Asn, and Ser, therefore, do not stabilize the
helix when at N1.