Bj. Stapley et al., ADDITION OF SIDE-CHAIN INTERACTIONS TO MODIFIED LIFSON-ROIG HELIX-COIL THEORY - APPLICATION TO ENERGETICS OF PHENYLALANINE-METHIONINE INTERACTIONS, Protein science, 4(11), 1995, pp. 2383-2391
We introduce here i, i + 3 and i, i + 4 side chain interactions into t
he modified Lifson-Roig helix-coil theory of Doig et al. (1994, Bioche
mistry 33:3396-3403). The helix/coil equilibrium is a function of init
iation, propagation, capping, and side chain interaction parameters. I
f each of these parameters is known, the helix content of any isolated
peptide can be predicted. The model considers every possible conforma
tion of a peptide, is not limited to peptides with only a single helic
al segment, and has physically meaningful parameters. We apply the the
ory to measure the i, i + 4 interaction energies between Phe and Met s
ide chains. Peptides with these residues spaced i, i + 4 are significa
ntly more helical than controls where they are spaced i, i + 5. Applic
ation of the model yields Delta G for the Phe-Met orientation to be -0
.75 kcal . mol(-1), whereas that for the Met-Phe orientation is -0.54
kcal . mol(-1). These orientational preferences can be explained, in p
art, by rotamer preferences for the interacting side chains. We place
Phe-Met i, i + 4 at the N-terminus, the C-terminus, and in the center
of the host peptide. The model quantitatively predicts the observed he
lix contents using a single parameter for the side chain-side chain in
teraction energy. This result indicates that the model works well even
when the interaction is at different locations in the helix.