Helix-Coil Transition Theory: from biophysics to biochemistry via probability ~ Lauraine Dalton

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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.

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The peptide bond has partial pi character its
geometry is planar. Ca is a member of two
planes.
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Rotation about Ca sigma bonds dihedral angles
phi and psipsiphipsiphi(yellow arcs)
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Ramachandran plot of allowed dihedral angles.
Steric clashes of side chains limit rotation.
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Hydrogen bond network of the alpha helix
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Helix-coil transition, a disruptive view of
unraveling
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Nucleation involves adjustment of 6 dihedral
angles elongation, 2
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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
• (.ccchhhhhhhhccc)
• s (.ccchhhhhhhcccc)

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Typical values of s and s s is approx 0. 001 s
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Helix macro dipole increases stability for long
helices (supports elongation s)
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Zimm-Bragg and Lifson-Roig concepts of weighting
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Sharpness of the transition, as calculated by
Schellman in 1958A coexistence of hhh and ccc
intermediate statesB h or c all or noneC
infinitely long helix
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Chou-Fasman rules of biochemistry
(probabilities)
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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-XX-carboxylate.
• Carboxylate (-) interacts favorably with helix
  macro dipole ()
• Ccap contributors are misfits P (bulky ring) and
  G (no side chain 2 H very flexible)

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Helices at work stable structures perform
mechanical tasks in lipid bilayer
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Biotin (Avidin) measurement tool
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