HelixCoil Transition Theory from biophysics to biochemistry via

Helix-Coil Transition Theory: from biophysics to biochemistry via probability ~ Lauraine Dalton • Protein primary, secondary, tertiary structure. • Alpha helix secondary structure properties. • Historical development of helix-coil transition theory (HCTT); from chemical physics to empirical biochemistry. • Helices at work; selected examples.

The peptide bond has partial pi character; its geometry is planar. Ca is a member of two planes.

Rotation about Ca sigma bonds: dihedral angles phi and psi phi (yellow arcs)

Ramachandran plot of allowed dihedral angles. Steric clashes of side chains limit rotation.

Hydrogen bond network of the alpha helix

Helix-coil transition, a disruptive view of unraveling

Nucleation involves adjustment of 6 dihedral angles; elongation, 2

Nucleation (difficult) & Propagation (facile) The equilibrium constant for nucleation (sigma) is typically 1000 times lower than for propagation (s). (…cccchhhcccc…. ) s= (…cccccc…. ) and the equilibrium constant (statistical weight) for adding another helical segment at the end of a stretch of helical residues is s = (…. ccchhhhccc…) (…. ccchhhhhhhcccc…)

Typical values of and s is approx 0. 001 * s

Helix macro dipole increases stability for long helices (supports elongation s)

Zimm-Bragg and Lifson-Roig concepts of weighting

Sharpness of the transition, as calculated by Schellman in 1958 A = coexistence of hhh and ccc intermediate states; B = h or c all or none C = infinitely long helix

Chou-Fasman “rules” of biochemistry (probabilities)

Helix initation and termination in proteins • J & D Richardson focused on Ncap and Ccap in analysis of 215 helical segment in known structures. • Current view is that Ncap motif consists of four residues S(T)XXE(D) = hydroxyl-XXcarboxylate. • Carboxylate (-) interacts favorably with helix macro dipole (+) • Ccap contributors are misfits; P (bulky ring) and G (no side chain; 2 H; very flexible)

Helices at work; stable structures perform mechanical tasks in lipid bilayer

Biotin (+Avidin) measurement tool