Determination of alpha-helix N1 energies after addition of N1, N2, and N3 preferences to helix/coil theory

Surveys of protein crystal structures have revealed that amino acids show u nique structural preferences for the N1, N2, and N3 positions in the first turn of the alpha-helix. We have therefore extended helix-coil theory to in clude statistical weights for these locations. The helix content of a pepti de in this model is st function of N-cap, C-cap, N1, N2, N3, C1, and helix interior (N4 to C2) preferences. The partition function for the system is c alculated using a matrix incorporating the weights of the fourth residue in a hexamer of amino acids and is implemented using a FORTRAN program. We ha ve 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 co ntents 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 NI by at least 1.4 kcal mol(-1) compared to Ala. The remaining a mino acids all have similar preferences, 0.5 kcal mol(-1) less than Ala. Gi n, Asn, and Ser, therefore, do not stabilize the helix when at N1.