Physics of Macromolecules

Navin Singh

November 2, 2010

1 STATISTICAL MECHANICS
1.1 A review
The foundation of statistical mechanics lies in the thermodynamics of ideal gases. This is the reason why
this subject in the beginning called it as Statistical Thermodynamics. Later on people realized the
power of this subject and its application in solving the equation of states and hence termed it as Statistical
Mechanics. With its diversity in the other fields now people often termed this subject as Statistical
Physics.
Starting with thermodynamics of ideal gas we will discuss more issues related with this subject.
In thermodynamics, we study the properties of the system at macroscopic level. For e.g. the pressure of
the gas is nothing but the collision of molecules with the surface. Temperature is nothing but the average
kinetic energy of all the molecules.
In statistical mechanics, we study properties of system at microscopic level. At microscopic level, one
has to deal with particles or system of particles. Problem with these kind of systems is their largeness. One
can not solve the dynamics of these particles with the help of Newtonian classical mechanics or quantum
mechanical equation. In those subjects, we treat system as a single particle and then solve its equation of
state.
In one mole of an ideal gas, there are 1023 number of particles. To solve the equation of state, one has
to solve 1023 number of equations !!. This is nearly impossible job even with most powerful computer in the
world. Here comes the power of statistical mechanics.
This subject is based on the theory of probability. According to this theory, we do not predict the exact
state of any occurrence, but ask the probability of occurring that event.
Let me take an example. An ideal gas having N number of particles occupying a space of V . If
the available energy to the system is E, the macroscopic behaviour of the system will depend on how at
microscopic level, this energy is distributed among the N number of particles. The distribution, as always,
have to obey certain rules. What are those rules?

X
i=N X
i=N
ni = N ni i = E (1)
i=1 i=1

which tells us that there are total N number of particles and ith particle is having energy i . Any distribution
which obey the above equation is possible. Others are discarded. Thus, there will be a large number of ways
in which this distribution is possible. Each of these ways is called as microstate of the system. The state
corresponding to any set of N , V and E is known as macrostate of the system. The number of ways is
denoted by a symbol Ω which is a function of N , V and E.
Interestingly, at this point, famous scientist, Boltzmann discovered with the help of many mathematical
formulations that the entropy of the system is somehow related with this microscopic quantity Ω(N, V, E).

1
He stated,
S = kB ln Ω(N, V, E) (2)
His argument was based on many probabilistic calculations which is beyond the scope of this discussion. Let
us see, whether this equation works or not? For a system in which there is a unique way to distribute the
above mentioned energy, the entropy of the system will be, S = kB ln Ω = 0, as Ω = 1. Any other form of
relation between entropy and Ω is not possible. As disorderness is more, randomness and hence the number
of ways in which the energy can be distributed is more.
What a simple and beautiful expression this is? This was a major breakthrough in the development of
this subject. This not only connect the thermodynamics with probability but also the macroscopic world
to microscopic world. This leads to formulation of ensemble theory which made this subject more vital and
diverse.

1.2 Phase Space

Let us introduce the concept of phase space which is required to calculate the quantities explaining the
behaviour of the system. Since in statistical mechanics we dealt with energy and its distribution, we need to
define a space which is more convenient to locate a microstate of the system. A space consists of momenta
and coordinate of the particle (they are also known as canonical conjugate quantities) is known as Phase
space. Just like to locate a particle in a Euclidean space you need space coordinates, to locate a particle
in phase space you need the information of its momenta and coordinates. A definite point in this phase
space exactly corresponds to one microscopic state of motion of the whole system. The temporal (i.e. time)
evolution of the system corresponds to one curve (q, p) in the phase space which is called the phase space
trajectory. This can be determined by Hamilton’s equation of motion as,
∂H ∂H
q̇i = ṗi = − (3)
∂pi ∂qi
Thus the energy of the system can be expressed in terms of Hamiltonian.
An example: Harmonic Oscillator
The Hamiltonian of a harmonic oscillator in one dimension is,
p2 1
H(q, p) = + kq 2 (4)
2m 2
where m is the mass of the particle and k the oscillator constant (spring constant). The phase space of this
√ p
system is nothing but an ellipse as, H(q, p) = E = constant, whose half-axes are a = 2mE and b = 2e/k.
Mathematically the phase space is denoted as, ω and an element in phase space is denoted as dω =
3N
d pd3N q.

1.3 Ensemble Theory

The aim of any theoretical attempts or equation is to validate the experimental observations. Experimentally
whatever is being observed it is a function of time. How one can emulates those experimental things using
a theoretical tool. In ensemble theory, we generate M number of systems which are mental copies of each
other and corresponds to each of the macrostate stated by (N, V, E). We define an expectation value of any
observable as,

hf i = the ensemble average of f ≡ the time average of (ensemble average of )f (5)

Since, the time and ensemble averages are completely independent things, one can restate the above equation
as,

hf i = the ensemble average of (time average of )f (6)

2
For a long period of time, the time average means we passed through all the members of ensemble. Thus,
taking ensemble average has no meaning. Hence,

hf i = long time average of f ≡ fexp (7)

1.3.1 Micro Canonical Ensemble

If a state of the system is defined by fix number of particles, volume and energy, the proposed ensemble is
called as Micro Canonical Ensemble. One can calculate the energy surface using equation discussed above
H(q, p) = E to find out the number of ways one can distribute the energy E among the particles N . Then
one can calculate the thermodynamical quantities from the relation S = kB ln Ω.

1.3.2 Canonical Ensemble

It is difficult to control or measure the energy E and hence to satisfy the relation H(q, p) = E some what
more tedious. In stead of energy we fix the temperature which is a controllable quantity and define the
macrostate of the system by N, V, T . This is the canonical ensemble. In this ensemble, energy can take any
value from 0 to ∞ and we ask the probability of finding a particle in an energy state Er . This probability,
Pr is found to be proportional to exp(−βEr ), where β = 1/kB T . The normalized probability is,

exp(−βEr )
Pr = P (8)
r exp(−βEr )

The denominator in the above equation is called as partition function which means sum over all possible
energy states and denoted by symbol, Z. The thermodynamical relation of this quantity is,

A(N, V, T ) = −kB T ln Z(N, V, T ) (9)

1.3.3 Grand Canonical Ensemble

If we do not impose the restriction over the number of particles, i.e. it can take any value between 0 to ∞,
the proposed ensemble is known as grand canonical ensemble. The relation between canonical partition
function and grand canonical partition function is

Ξ(z, V, T ) = z N Z(N, V, T ) (10)

where z is known as the weight factor or fugacity corresponding to exchange of particles and z = exp(βµ)
where µ is the chemical potential.

1.4 Some applications

With these preliminaries knowledge of the subject one can explain various interesting phenomena around us.

• Bose Einstein condensation

• The specific heat of the solids

• The paramagnetism

• Black body radiation

• The conformation of polymers

• The helix coil transition in proteins and DNA

3
1.5 Problems
1. Consider a system A having N number of particles, occupying V space and having energy E. Calculate
the number of microstates available to the system and hence the entropy of the system.
Sol: Let us consider M identical systems in contact with each other. Let the number of systems in
the quantum state ψi be ni out of M . There are n1 systems in ψ1 state, n2 systems in ψ2 state and so
on. The number of ways in which one can arrange n1 systems in ψ1 states etc. can be written as,
M! M!
Ω= = Qi=M (11)
n1 !n2 !n3 !n4 !n5 !.. i=1 ni !

The entropy of the system is,

" # " #
X X
SM = kB ln Ω = kB ln M ! − ln ni ! ≈ kB M ln M − ni ln ni
i i
" # " #
X X X n 
i
= kB ni M − ln ni = −kB ni ln
i i i
M
" # " #
X  ni  n 
i
X
= −kB M ln = −kB M pi ln(pi ) (12)
i
M M i

Entropy per particle can be written as,

SM X
S= = −kB pi ln(pi ) (13)
M i

If there are Ω quantum states available to the system, the probability to be in one of these states is
1
pi = Ω. Thus, the entropy per particle will be,
X 1 1
S = −kB ln = −kB ln Ω (14)
i
Ω Ω

√
2. For an arbitrary system, the number of microstates is given as, Ω = a exp(b EV ), where a and b are
some constants. By working out the steps, find out the relation between the energy and the temperature
of the system. What will be the value of the energy for which the temperature of the system will be
zero?

3. A system at 300 K temperature is releasing a heat of 10−6 J and is adding the same to a system at 299
K. How much is the total entropy changed during this conversion? By what factor does the number of
accessible states increase?

4. Find out the temperature of a system whose microstates are given as ω = A exp[γ(EV )1/2 ], with γ as
some constant. For which value of energy, the temperature of the system will be zero?

5. The entropy of black body radiation is given by the formula, S = 43 σV 1/4 E 3/4 where σ is some constant.
Determine the temperature of the radiation and show that P V = 13 E.

6. Three energy levels having energies, E1 = 0 J, E2 = 1.4 × 10−23 J, E3 = 2.8 × 10−23 J.

4
2 Conformation Dependent Properties of Polymers

2 i−1
1

φ
i−1
n

This is an hypothetical polymer chain in which circle denotes the molecules while bonds are numbered from
1 to n. Diehedral angles are numbered from φ2 to φn−1 . Angles φ1 and φn are meaningless.
The reference angle φ = 0 corresponds to the trans conformation of the polymer chain.

2.1 End to End distance

ree

The end-to-end distance vector r may be calculated as the sum of the bond vectors, li

X
N
r= li (15)
i=1

To find out the magnitude of this vector,

X
N XN X
N X
N X
r2 = r · r = ( li ) · ( lj ) = li · lj = nl2 + 2 li · lj (16)
i=1 j=1 i=1 j=1 i<j

Thus, the mean square end-to-end distance will be,

X
hr2 i = nl2 + 2 hli · lj i (17)
i<j

Thus the calculation of end-to-end distance is reduced to find out the average projection of every bond vector
on the other bonds.

2.2 The Freely Jointed Chain Model

The freely jointed chain

model (random walk)

Figure 1: The freely jointed chain model. This is also known as Ideal or Random walk model.

This is also known as Random walk chain or Ideal chain model. In this model, each and every bond
vector is uncorrelated with other one. Using this model the calculation of end-to-end distance vector is little

5
bit simple as hli · lj i = 0. Why? Since each bond vector is free to rotate in the free space with the same
angle, the average of their scalar product will be equal to average of cos(θ) which is zero.
Thus,
hr2 i = nl2 (18)
hr i
2
The ratio nl2 is known as characterstic ratio which measures the stiffness of the chain.

2.3 Radius of Gyration

The radius of gyration is defined as the root mean square distance of an array of atoms or group of atoms
or groups from their common center of gravity. For a chain of n + 1 identical atoms joined by n bonds, if
rij
i j

ri rj

Centre of mass

Figure 2: The radius of gyration.

RGi is the distance of skeltal element i from the centre of gravity, then,

1 X 2
n
2
RG = R (19)
n + 1 i=0 Gi

Let us consider a polymer composed of (n + 1) monomers. The ith monomer will be having coordinate
PN
(xi , yi , zi ) and has mass mi . The centre of gravity is a point where i=1 mi ri = 0, where,ri is a vector from
P
the centre of mass to the unit i. For idential monomers, i ri = 0. Now,

X 1 XX
N
2
rij = rij · rij (20)
i<j
2 j=0 i=0

where, rij is the vector between i and j vectors. Also, rij = 0 for i = j and ri − rj for any i & j. Thus,

X 1 XX
N
1 XX 2
N
2
rij = (ri − rj ) · (ri − rj ) = (r + rj2 − 2ri2 · rj2 )
i<j
2 j=0 i=0 2 j=0 i=0 i

XX
N
= (n + 1)2 2
RG − ri · rj = (n + 1)2 RG
2

j=0 i=0

P P
Since, j=0 rj2 = i=0 ri2 = (n + 1)RG
2
(defined earlier), also the ith and j th monomers are uncorrelated,
P P P P
thus, j=0 i=0 rj · ri = j=0 rj · i=0 ri = 0. This will give,
X
2
rij = (n + 1)2 RG
2
(21)
i<j

2.4 Distribution of End to End distance

Since polymer is a flexible object, there are enourmous configuration or a distribution of end-to-end distance
vector. Statistically, it is of considerable interest if we find out the distribution of this vector. In cartesian
coordinate system, we have to compute the average projection of a bond vector. By assuming that each bond
will be having either positive or negative orientation, consider the average projection of length l. If θ is the

6
 y

l lsinθ

θ x
lcosθ
ldθ

Figure 3: The bond vector and its projection along x-axis.

angle between the bond vector and the z-axis, the mean square projection length lx2 will be l2 hcos2 (θ)i. Thus
to find out the average projection we have to find out the canonical average of cos2 (θ). Since distribution
of cos(θ) is equally probable in all direction, the number of vectors lying in the region θ and θ + dθ will
be determined by the area of the annular ring which is obtained by rotating the bond vector about the
x-axis with the fixed angle θ between the vector & x-axis. This area is 2πl2 sin(θ)dθ. Thus, the mean square
projection length will be, Rπ
l2 cos2 θ(2πl2 ) sin θdθ l2
hlx2 i = 0 Rπ = (22)
2
2πl sin θdθ 3
0
√ √
Thus, the average root-mean square projection along a given axis is ±l/( 3) Now the average steps l/ 3
along the chosen axis occur with random statistics in negative and positive directions. If there are N bonds,
i.e. N steps, the distance traversed along x-axis will be,
(N1 − N2 )l
x= √ (23)
3
where, N1 is the step in positive direction, while N2 is the step in -ve direction. Also N = N1 + N2 . The
probability W (N1 , N2 , N ) of N1 & N2 steps out of total steps N will be,
1 N!
W (N1 , N2 , N ) = N
(24)
2 N1 !N2 !
1 N!
where, 2N
is the probability of generating a particular sequence of positive and negative steps while N1 !N2 !
represents the number of particular sequence of steps.
Using Stirling’s approximation which states that,
1 1
ln N ! ≈ N ln N − N + ln(2π) + ln N (25)
2 2
and under the condition that N is large and defining M = N1 + N2 , we can solve the equation for probability
(the detailed derivation is left for you to work out). Thus,
     
1 2 N M2 M 1 + M/N
ln W (N1 , N2 , N ) = ln − ln 1 − − ln (26)
2 nπ(1 − M 2 /N 2 ) 2 N2 2 1 − M/N
For large x, we have,  
1+x
ln ≈ 2x & ln(1 − x) ≈ −x (27)
1−x
Using this, one can argue for large N (N >> M ) the eq.(26) can be re-written as,
r ! r !
2 N M2 M 2M 2 M2
ln W = ln + − = ln − (28)
Nπ 2 N2 2 N Nπ 2N

7
Hence, r  
2 M2
W = exp − (29)
Nπ 2N
Gaussian distribution.
Let us calculate the probability in terms of distance travelled. Defining the distance variable as

ml 3x2
x = √ ⇒ M2 = 2 (30)
3 l

In terms of distance variable one can ask the probability per unit interval of distance that x takes between
x and x + dx. For fixed N , the value of M changes in units of two as, for M = N1 + N2 . This means that x
W (M,N )
changes by ± √2l3 , the relation W (x, N ) = interval requires an interval equivalent to two units of M , i.e. 2l
√
3
.
√ r  
3 3 1 3x2
W (x, N ) = W (M, N ) = exp − (31)
2l 2πN l 2N l2

With similar aruguement we can write for W (y, N ) & W (z, N ). Thus,
 3
B
W (x, y, z)dxdydz = √ exp(−B 2 R2 )dxdydz (32)
π

3

1/2
where, B = 2N l2 & R 2 = x2 + y 2 + z 2

2.5 Statistical Segment

We have defined the characterstic ratio as,
hr2 i
CN = (33)
N l2
for FJC CN = 1. For real chain, for large N , CN approaches as C∞ .
For random walk or FJC model, hli .lj i = 0 for all i 6= j. In case of real chains, hli .lj i → 0 for sufficiently
large | j − i | which means that bonds separated by sufficiently large distance are randomly oriented.
This gives the concept of statisical segment for real chains. This means that large polymeric chains can
be approximated as FJC where bond lengths are replaced by statisical segments. In the limiting case,

hr2 i
C∞ = ⇒ hr2 i = C∞ N l2 (34)
N l2
in terms of statistical segment,
hr2 i = Ne le2 (35)

where, Ne is the number of statistical segments while le is the length of that segment. Also, the maximal
length of the chain will be, rm = Ne le = f N l, where, f is some number between 0 & 1 (equal to cos(θ/2)
for even number N ). Solving all these equations will give us,
 2   
f C∞
Ne = N & le = l (36)
C∞ f

This means that Ne ∝ 1

C∞ and le ∝ C∞ . Remember, the C∞ signifies the stiffness in the chain.
An example
For polymethylene, f = 0.83, C∞ = 6.7. This implies that Ne ≈ 0.1N ⇒ N
Ne = 10. This means that
“statistical segment” spans approximately 10 bonds.

8
 a

l1
r

Figure 4: The average projection of r on the first bond vector.

2.6 Persistence Length

The average projection of end-to-end distance vector r on the first bond of the chain l1 .
  X N
l1
a=h . li i (37)
l1 i=1

It is a measure of the length over which the chain persists in the same direction, as the first bond. In general,
  X N
li
a=h . lj i (38)
li j=1

For chain composed of identical bond length, l, the persistence length is closely related to the limiting
characterstic ratio C∞ .
X
N X
N X
N X
N X
N
hr2 i = N l2 + 2h (li .lj )i = N l2 + 2h (l1 .lj )i + 2h (li .lj )i (39)
j=i+1 i=1 j=2 j=i+1 i=2

As per definition of persistence length, as define in eq. (37), the second term in eq. (39) can be written as,

X
N
h (l1 .lj )i = al − l1 .l1 = al − l2 as N → ∞ (40)
j=2

Similarly we can partitioned the third term in eq. (39) for i = 3 and so-on. This simply means that the
third term in eq. (39) can be replaced by 2(n − 1)(al − l2 ). Thus,
 
2a
hr2 i = N l2 − 1 = C∞
l
l(C∞ + 1)
a = (41)
2
This ratio gives us a physical feeling of limiting characterstic ratio.

2.7 Porod Kratky (Worm Like Chain) model

From various studies it has been found that long DNA chain is not like a rod but behaves like worm. It is
rod like at shorter length but as the length of the chain increases its properties are more closer to a worm.
To study the elastic response of dsDNA chains, a simple model was proposed by Porod and Kratky
which is also known as Worm like chain (WLC) model. This model assumes the chain as a continuously
curving chain. The direction of curvature at any point is assumed to be random. In this model, there are
x hypothetical bonds of length lb are assumed. Each bond makes an angle θ with its neighbour and free to
rotate in the space. The average projection, ρ, of the end-to-end distance vector r on the first bond is,
X
x−1
ρ = lb (cos θ)k (42)
k=0

9
 θ
b

Figure 5: The worm like chain model.

For large x, ρ → a and the summation conveges to [1 − cos θ]−1 . Thus,

lb
a= (43)
1 − cos θ
If we reduce the lb in such a way that a and the contour length Lc are held constant at their pre-determined
values. In that case, lb → 0 and θ → 0 which means that 1 − cos θ → 0 and x → ∞. Hence,
lb lb
= =a (44)
1 − cos θ − ln[cos θ]

This will give, cos θ = exp(−lb /a). Here we have used an assumption that ln x ≈ x − 1 for x ≈ 1. In this
limiting case, the summation (discrete) can be replaced by integration (continuous) as,

X
x−1 Z x Z Lc
ρ = lb exp(−klb /a) = lb exp(−klb /a)dk = exp(−L/a)dL = a[1 − exp(−Lc /a)] (45)
k=0 0 0

where, the summation is converted into integration for small lb and x → x − 1 for x >> 1; L = lb k.
Let us try to establsih a relation between end-to-end distance vector and the persistence length. From
figure one can infer that r.dr = ρdLc . Taking differential of both sides,

dc = 2hr.dri = 2ρdLc = 2a[1 − exp(−Lc /a)]dLc (46)

Integrating both sides for the complete chain, as,

Z Lc  
a
hr2 i = 2a [1 − exp(−Lc /a)]dLc = 2aLc 1 − {1 − exp(−Lc /a)} (47)
0 Lc
In the limit of large Lc ,
hr2 i
= 2a (48)
Lc
while for Lc /a < 1, we have " #
 2
1 Lc 1 Lc
hr i =
2
L2c 1− + + .... (49)
3 a 12 a
One can draw the following conclusions on looking on these two limiting case.

• One can argue that for Lc << a (which means contour length is much smaller than the persistence
length) hr2 i ≈ L2c . Thus chain behaves rod like.

• For very large contour length the effect of curvature plays the role and

hr2 i 2a
= (50)
L2c Lc

An example For dsDNA, one can calculate the contour length Lc . Let us take a dsDNA of 1000 bps.
This chain has a = 450 Å. One can estimate that contour distance below which DNA is rod-like in solution
corresponds to a value of 0.1. This will give an estimation of contour length as 135 Å.

10
 Figure 6: The schematic of bonding for the formation of α-helix. The NCC model.

3 Helix Coil transition

It is proved through X-ray crystallographic, infrared spectra, optical rotational viscosity etc studies that
polypeptide can form α-helical in the crystalline as well as in solution. During α helix formation the
hydrogen bonding between oxygen of carboxyl group at i + 4 & hydrogen of amide group at i if formed. The
rotation angle φ and ψ [between C-C and C-N] remains fixed at +50 (left handed) and -50 (right handed).
In solution at some values of physical parameters, the polypeptides are in α helical form but with the
change in these physical parameters (temperature, solvent composition, pH etc.) this form disrupts. Poly-
i-glumate have ionizable carboxyl group and is a function of pH of the solution. Thus conformation of this
polymer varies with variation in pH of the solution.
These plots show that as the value of pH is increased there is a sharp change in the optical rotation,
intrinsic viscosity and continuous change in ionization. All these changes reveals that the conformation of α
helix form of poly-Lglumate changes to some other form, may be random coil. From ooptical rotation and
intrinsic viscosity curve, signature of random coil appears as thier values at higher pH is smaller. Second
iportant information is that they are showing the transition to be “co-operative”, i.e. all or none kind. The
transition from helix to coil can be made by changing the temperature of the solution. The formation of
helix depends on the chain length.

3.1 Molecular Mechanism of the transition

From experimental obsevation it is clear that transition from coil to helix and vice versa is a sharp transition.
There is a co-operativity in the transition. What is the reason behind this co-operativity?
Let us try to understand the mechanism involve at molecular level.
Hydrogen bonding is between C = O · · · H − N . To make a hydrogen bond (the first one), six dihedral
angles have to move. When chain is in random coil configuration all set of φ, ψ configuration are possible.
To make this bond the change in entropy is large. However, making the second and successive bonds change
in entropy is low. Also to minimise the end effects the length of helix should be large.

3.2 Thermodynamics of the transition

The idea discussed here was proposed by John Schellman in 1955. He made several assumptions to explain
the thermodynamical behaviour of this transition. The assumptions are:

• Each chain is assumed to be either all helix or all coil, no intermediate structure.

• The free energy change for converting coil to helix is

∆Gr = ∆Hr − T ∆Sr (51)

where, ∆Hr is the change in enthaply in forming a hydrogen bond while ∆Sr is the loss in entropy for
the same.

11
 Figure 7: Six dihedral angles have to rotate for first bond, while only two bonds are required to rotate.

To calculate the net change in the Gibbs free energy of the system one can argue that it should be ∆GT =
N ∆Gr , which is not correct for polypeptide chain. In this case we have to look at the microscopic level
which will give us, that net change in the free energy will be,

• At the ends four bonds (4 of carboxyl and 4 of amide) are still free which will reduce the net enthaply
as (n − 4)∆Hr .

• The entropy contribution from the two ends will increase the net entropy as (N − 2)∆Sr

Thus, the net change in Gibbs free energy will be

∆GT = (N − 4)∆Hr − (N − 2)∆Sr (52)

The equilibrium constant K for the reaction is,

[Helix]
K = cbN = ⇒ ∆GT = −RT ln K = −RT ln c − N RT ln b
[Coil]
   
∆GT ∆Hr T ∆Sr ∆Hr ∆Sr ∆Hr ∆Sr
− ln c − N ln b = = (N − 4) − (N − 2) =N − − 4 −2 (53)
RT RT RT RT R RT R

Equating RHS & LHS will give,

 
∆Hr ∆Sr
b = exp − + (54)
RT R
 
∆Hr ∆Sr
c = exp 4 −2 (55)
RT R

Point to note here is that as predicted by eq (53) for large N , small change in b can cause sharp change in
K. The parameter c reflects the deficit of hydrogen bonds at the ends while b for bonding.
During the folding of polypeptides, is there a critical number below which the polypeptide can not fold?
Let us try to find out the answer. If we believe that there is a temperature T = Tm at which the unfolded
state changes to folded state (or vice-versa) at which the Gibbs free energies of helix & coil states are equal.
At this temperature ∆GT = 0 and K = 1. Putting these in eq.(52) will give

(N − 4) ∆Hr
∆GT = 0 = (N − 4)∆Hr − (N − 2)Tm ∆Sr ⇒ Tm = (56)
(N − 2) ∆Sr

12
This is reason why the minimum number of residues should be 5, otherwise Tm will be negative which is
unphysical.
At N = 5
1 ∆Hr ∆Hr
Tm = for N → ∞ Tm ∼ (57)
3 ∆Sr ∆Sr
i.e. variation of Tm is independent of N . Check out the value of N for which II part of eq. (57) holds.
Let us observe the sharpness of the transition. If we plot θ (fraction of helicity) as a function of temper-
ature, the slope at Tm will give the information about the sharpness of the transition. Since, equilibrium
constant is
[Helix] θ ∆Hr
K= = ⇒ ln K = ln θ − ln(1 − θ) = −(N − 4) (58)
[Coil] 1−θ RT
Differentiating both sides with respect to temperature, we have
     
1 dθ 1 dθ ∆Hr 1 dθ
+ = (N − 4) = (59)
θ dT T =Tm 1 − θ dT T =Tm RT 2 θ(1 − θ) dT

At T = Tm , θ = 21 . Substituting these along with the value of Tm from eq.(56), we have,

dθ 1 (N − 2)2 ∆Sr2
= (60)
dT 4 (N − 4) ∆Hr

which means slope of the θ vs temperature varies with N . However this model oversimplify the actual
phenomenon. The assumption of all or none is litte bit superficial as it is found that there are intermediate
states during helix to coil (or vice versa) transition.

3.3 Partition function for the Simple Chains

The partition function is useful tool to estimate the energy of helix-coil transition. In this method we calculate
all possible states in which system has finite probability to exist. A partition function Z for molecule can be
defined as,
X 1
Z= gi exp(−βi ) where β = (61)
i
kB T

Here, gi is the statisical weight (number of states that have energy i ), i is the energy of ith state. gi is also
known as degeneracy of the ith state.
Let us consider a hypothetical chain consisting of four elements A in which there are two states A+ and
A− are possible. The possible conformation if the chain will have, A+ A− A− A+ , A+ A+ A− A− , and so-on.
Taking care of directionality in the chain A+ A+ A− A− and A− A− A+ A+ will be treated as two states.
The possible conformation

• All A− A− A− A− states will contribute as Z0 .

• All A+ A− A− A− states will contribute as Z1 . There are 4!

3!1! = 4 number of ways to realise it.

• All A+ A+ A− A− states will contribute as Z2 . There are 4!

2!2! = 6 number of ways to realise it.

• All A+ A+ A+ A− states will contribute as Z3 . There are 4!

3!1! = 4 number of ways to realise it.

• All A+ A+ A+ A+ state will contribute as Z4 . There is a unique way to realise this state.

Thus, the partition function will be,

Z = Z0 + 4Z1 + 6Z2 + 4Z3 + Z4 = Z0 [1 + 4K1 + 6K2 + 4K3 + K4 ] (62)

Zi
where, Ki = Z0 is known as equilibrium constant.

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 For most of the calculations we do not require the value of Z0 . This will be more clear with an example.
Let us find out the fraction of molecules with a particular number of A+ elements. If θ2+ is the fraction of
two A+ molecules,

6Z2 6K2 Z0
θ2+ = = (63)
Z Z0 [1 + 4K1 + 6K2 + 4K3 + K4 ]
6K2
= (64)
1 + 4K1 + 6K2 + 4K3 + K4
One can assume that Z0 = 1 as reference state and the change in free energy can be calculated for converting
A− to A+ . Thus, ∆Gi = −RT ln Ki . To convert an A− state to A+ , we need,
   
∆G 2∆G
K1 = exp − = s and K1 = exp − = s2 and so − on (65)
RT RT

where, s is the statisical weight. Thus,

X
4
Z = 1 + 4s + 6s2 + 4s3 + s4 = Ωi si = (1 + s)4 (66)
i=0

where, Ωi is the number of ways of putting iA+ elements in a chain of four unit. Using bionomial expansion
4!
method, one can argue that it is nothing but Ωi = (4−i)! . Thus, the partition function is now expressed as a
simple sum of terms involving powers of a single statistical weight parameters s. which is assigned to every
A+ element, with a factor of unity assigned to each unit in the A+ state.
Rules for constructing the partition function
In general the partition function for these kinds of systems are generated with the help of following steps:

• Consider all possible conformations of the chain.

• Establish a reference state for a chain element, and assign this state a statistical weight of unity.

• For each conformation of the chain, assign an appropriate statistical weight for each element that is
not in the reference state.

• Construct the partition function by summing over all conformations, with appropriate products of
statistical weighting factors assigned to each conformation.

3.4 The Zipper model

In this model, each residue has two possible states, helix (h) or coil (c). Their existence in a given confor-
mation however has to follow some restrictions. Initiation of helix state can occur at point, but all the helix
state should be in one stretch. That is, hhhcccc, ccchhhhhccc like states are allowed but hhcchhhhccc kind
of states are not allowed.
In an α-helix, out of m residues, only m − 2 residues adopt a unique value of φ and ψ. There will be
m − 4 number of hydrogen bonds are possible in the complete chain. In this model, we consider n units
which can exist in either helical or coil state. One can construct the partition function for this chain by the
method discussed below.
Let us put all coil configuration as the reference state and assign it a statisical weight of unity. If s is the
statisical weight or equilibrium constant in converting one coil state into a helix state at the end of helical
segment, then,
· · · cccchhhhhhcccc · · ·
s= (67)
· · · cccchhhhhccccc · · ·
This is the propagation step. The inititation of a helical section with an all coil chain is much more difficult
than the propagation. Growth or propagation is relatively easier that nucleation or inititation.

14
 Assume that σs be the equilibrium constant (σ << 1) for the nucleation, then

· · · ccchccc · · ·
σs = (68)
· · · ccccccc · · ·
Thus, the partition function will be,
X
n
Z =1+ Ωk σsk (69)
k=1

where, Ωk = (n − k + 1) represents the number of ways of putting k helical units together in one sequence.
P
This one can show by the method of induction. The term must be summed are of the forms k sk and
P k
k ks , where the sums are taken from k = 1 to k = n. Thus,

X
n X
n X
n X
n X
n
Z =1+n σsk − kσsk + σsk = 1 + (n + 1)σ sk − σ ksk (70)
k=1 k=1 k=1 k=1 k=1

The second term in the eq.(70) is a geometric term whose sum is

X
n
sn+1 − s s(sn − 1)
sk = s + s2 + s3 + ... + sn = = (71)
s−1 (s − 1)
k=1

Also,
 
d X k X k
n n
s
s s = ks = (nsn+1 − (n + 1)sn + 1) (72)
ds (s − 1)2
k=1 k=1

Thus the partition function will be,

 
σs2
Z =1+ [sn + ns−1 − (n + 1)] (73)
(s − 1)2

Fractional Helicity
The fractional helicity θ can be evaluated by partition function. The probability p(k) that the chain has
k helical units is,
(n − k + 1)σsk
p(k) = (74)
Z
The fractional helicity θ can be evaluated now as,

1X 1 X
n n
<k> s ∂Z 1 ∂ ln Z
θ = = kp(k) = k(n − k + 1)σsk = = (75)
n n nZ nZ ∂s n ∂ ln s
k=1 k=1
 
 ns  − (n + 2)sn+1 + (n + 2)s − n 
n+2
σs
=  (76)
n(s − 1)3
1+ σs
2 (sn+1 − (n + 1)s + n)
(s−1)

Thus, for s = 0 ⇒ θ = 0 while for s = ∞ ⇒ θ = 1. For long chains, s → 1, θ → 0.5. s can be changed by
temperature or pH of the solution.
This model is good for short chain as the basic assumption of this model upto some limit, is valid. For
longer chain, this model fails to explain the qualitative behaviour of the transition.

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