ADDITION OF SIDE-CHAIN INTERACTIONS TO MODIFIED LIFSON-ROIG HELIX-COIL THEORY - APPLICATION TO ENERGETICS OF PHENYLALANINE-METHIONINE INTERACTIONS

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.