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Loukas Petridis
Monday April 7th 2008
Aim
Introduce simplest theory of helix-coil transition of short polypeptides
Demonstrate one example of pen and paper theoretical physics
Outline
State the problem
Recap of alpha-helix and random coil
Statistical Mechanics applied to this problem
Derive the model, examine number of h-bonds
Experimental investigation
Statement of Problem
amide group:
rigid planar structure
freedom of rotation of alpha-C
define helical residue:
dihedral angles of C characteristic of helix (C-N-C-C = 97)
define coil residue: dihedral angles not these of helix
Thermodynamics of Transition
single residue transition from coil to helix
initial approach, to check if helix forms or not
use Gibb's free energy change G:
free energy
G = H - TS
enthalpy
entropy
Statistical Mechanics
each residue can be in either of two states: h or c
Partition Function
to obtain average quantities must compute partition function Z
(sum over all microstates)
Z = e
G { h , c } / k B T
{h , c }
eG {h , c } / k
P {h , c }=
Z
n = n P n g n
n
n:
number of h-bonds
P(n): probability having n h-bonds
gn: degeneracy
Z = e
G { h , c } /k B T
{h , c }
Approximations:
cchhhhhh allowed
only length of sequence matters, not its position on the chain- residues do not interact
1 if in coil state
s if the first helical residue
s for all other helical residues
Temperature Dependance
energy change per monomer upon helix formation: G = H TS
s related to probability of a residue being helical
depends on G
H and S <0
0.2575
0.255
s=e G / kT =e H / kT S
0.2525
2 G interface / kT
=e
=e 2 H / kT
s (a.u.)
0.25
0.2475
0.245
0.2425
0.24
0.2375
0.235
0.2325
0.23
270
280
290
300
310
Temperature (K)
320
330
340
Ludwig Boltzmann
Gelatine
polypeptides (300-4000 amino acids)
extended left-handed proline helix
forms gels below about 35C
dissolve at low temperature to give
'melt in the mouth' products
N=4 example
microstate cccc chhh hhhc hhhh
1
s3
s3
s4
stat weight
0
1
1
2
n
partition function:
Z =12 s s
remaining (n-1)
helical residues
1st h
N 2
Z =1 N n1 ss
n1
n=1
degeneracy
n: h-bonds
N: residues
N 2
Z =1 N n1 s
evaluation of sums
n=1
N 2
N 2
n
Z =1 N 1 s n s n =1
n=1
n=1
s
N 1
[
s
N 1 s N 2]
2
s1
N 2
n=
n N n1 s n
n=1
evaluation of sums
N 2
1 N n1 s n
n=1
s
N
N 1
[
N
2
s
N
s
Ns N 2]
3
dZ 1 s1
n = s
=
ds Z
s
N 1
1
[
s
N 1 s N 2 ]
2
s1
=
max number
of possible hbonds
n
N 2
Approximations Revisited
Transition
fit parameters s, and
H from calorimetry
chain length = 50
chain length = 14
assume
temperature independent
s: -kT ln s = G
Recap
Statistical Mechanics theory of helix-coil
residue either h or c
no interaction between residues
one sequence approximation
nucleation and growth approach
Evaluate
partition function
average number of h-bonds
Experiments
CD to find helical fraction
good agreement with theory
fit data to obtain parameters and s