Transcript Helix-Coil Transition Theory: biophysics introduction ~ Lauraine

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
psi
phi
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=
(…ccccccccccc….)
and the equilibrium constant (statistical weight) for adding another
helical segment at the end of a stretch of helical residues is
s =
(….ccchhhhhhhhccc…)
(….ccchhhhhhhcccc…)
Typical values of  and s
 is approx 0. 001 * s
Residue
Glycine
Alanine
Serine
Leuc ine

1 E-5
8 E-4
7.5 E-5
33 E-4
s
0.62
1.06
0.79
1.14
Remarks
Glycine excep tiona l range of 
Small vo lume of side cha in
Like alanine but one -OH
Flexible hyd rocarbon side cha in
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