Department of Physics

Indian Institute of Technology

Kharagpur-721302, West Bengal, India
Subject No. PH60206 (Physics of Biomacromolecules) Duration: 55 Min each
Instructor: A. N. Gupta
Lecture # 7, # 8, & # 9
Boltzmann Distribution and its Applications
I shall consider some examples of group of identical particles with some total energy where particles can
exchange energy with one another. You need to distribute the total energy, 8∆E between 6 particles. I
N!
shall look into the each macrostate and their microstates (Ω = ) for a discrete case.
n0 ! n1 ! n2 ! ..
Let us consider 6 identical particles with total 8∆E, with (0, ∆E, 2∆E... 8∆E).
If you consider ∆E → 0 it will be continuous distribution.

Macrostate 1;
FIVE particles are with ZERO energy and ONE particle with 8∆E. The number of microstates would be
6!
for this macrostate is, Ω = = 6.
5! 1!
Macrostate 2;
FOUR particles are with ZERO energy and ONE particle with ∆E and ONE particle with 7∆E. The
6!
number of microstates would be for this macrostate is, Ω = = 30. Here you can distribute the two
4! 1! 1!
particle such that the sum of their energy will be 8∆E.

4 particles are at zero energy and other two particles are at 4∆E. So, for this macrostate, the number of
6!
microstates would be, Ω = = 15.
4! 2!
X X X
n(Ei ) = nij Pj = gi P (Ei ) = B e−β Ei ; where gi is statistical weight; and N = n(Ei ).
j i i

If energy associated with some state is E then the frequency with which that state occur or probability of
its occurrence is proportional to e−βE . You can consider 2-D square grid of two different number of grids
at lower and higher temperature. Estimate the number of microstates individually and when they are in
contact. There is some chance of hopping of particles from smaller temperature to the higher temperature
grid, but as the size of the grid increase the chances of hopping tends to zero.

The velocity distribution of gaseous molecules follows M-B distribution.

e−βEi
r
m mv 2
X
f (v) = e− 2kT .⇒ f (v1 + v2 ) = f (v1 ) + f (v2 ) . Pi = P −βEi , with Pi = 1.
2πkT i e i
!
−βEi
P
E i e ∂ X ∂ ∂
Ē = U = Pi −βEi = − ln e−βEi = −k ln Z = (A/T ).
i e ∂β i
∂(1/T ) ∂(1/T )
where, A = −kT ln Z + T ϕ(V, N1 , N2 ..) ⇒ Ē = U = A + T S. Other thermodynamical variables can
be written,
∂ ∂ ∂
S=− A; p = − A; µ1 = A.
∂(T ) ∂(V ) ∂(N1 )
Z ∞
For a continuous system, Z = W (E) e−βE dE; where W (E) is density of state. This is Laplace transform
E0
of the density of state and the partition function, and vice-versa.
PH60206 by A. N. Gupta Lecture # 7, # 8, & # 9 2

Application:
1 √
Probability, P (E) = W (E) e−βE ; The energy fluctuation would be, δE ∝ N .
Z

1. Two state system:

Suppose a system can exist in 2 states, E, and E + ∆E. You can write,

P1 e−βE
= −β(E+∆E) ; and P1 + P2 = 1.
P2 e
1 1
⇒ P1 = −β∆E
; & P2 = .
1+e 1 + eβ∆E
Plot these probability with temperature.
At low temperature, system lies in the lowest state E and as T increases, both states becomes equally likely.
PH60206 by A. N. Gupta Lecture # 7, # 8, & # 9 3

2. Two states (open and closed) in the ion channel

The figure below, shows the ionic current (consisting of positive potassium ions)
as a function of time flowing through a single biological component (called an
ion channel) when a potential difference of 60 mV is applied across it. When the
ion channel is open, ions can flow through it the current is 4 pA (1 pA = 10−12
A) and when the ion channel is closed, the current is zero.

You can model the ion channel as two state model with a barrier:
PH60206 by A. N. Gupta Lecture # 7, # 8, & # 9 4

Chemical equilibrium can be achieved if rate is same between states.

S2 ⇄ S1; with k+ and k− as forward and backward rate respectively.

k+ = C e−βEB ⇒ N2 k+ = N2 C e−βEB .

Similarly, k− = C e−β(∆E+EB ) ⇒ N1 k− = N1 C e−β(∆E+EB ).

N2,eq P2
In the equilibrium, N1k− ⇄ N2 k+ ⇒ = e−β∆E = .
N1eq P1

At equilibrium, the distribution of particles ONLY depends on the energy dif-

ference between states.

What is the significance of barrier? How long it takes to reach equilibrium?

The energy barrier affects the rate. From Boltzmann;
rate (2 → 1) = (attempt rate) x (probability of jumping barrier from 1 → 2).

k+ = v e−βEB .

We learnt that the larger the barrier, the longer it will take to reach equilibrium.

On average how long will the particle spend in each state (Dwell time)?

gone
At time ‘t’ there are N (t) molecule in S2 after time ‘dt’ the remaining molecule
will be k+dtN (t).
So, N (t + dt) = N (t)(1 − k+dt); Let N (0) = N0 ;⇒ N (t) = N0e−k+t.

P2→1(t)dt =(Prob. of surviving in state 2 till t )× (prob. of jumping in dt).

 
N (t)
P2→1(t)dt = k+ dt = k+e−k+t ⇐ Exponential distribution.
N0
PH60206 by A. N. Gupta Lecture # 7, # 8, & # 9 5

3. pulling a hairpin molecule (unfolded and folded states)

PH60206 by A. N. Gupta Lecture # 7, # 8, & # 9 6

Molecular Interaction
It may be attractive or repulsive forces between molecules and between non-bonded atoms. The processes
of melting, boiling, sublimation, unfolding, assembly involve changes in molecular interactions.
Force in nature
We will discuss one by one in separate class.

■ Strong interaction
Strong/Weak interaction: Acts between elementary particles; very short range: less than 10 fm;
Belongs to nuclear and high energy physics

§1. Covalent bond: sharing of electrons between two atoms (single, double, triple)
§2. Ionic bond: electrostatic interaction between ions of opposite charge
§3. Resonance bond: de-localization of some covalent bonds
§4. Metallic bond: sharing of electrons between several atoms

■ Weak interaction

§1. Van der Waal types

(a) polar-polar
(b) polar-non polar
(c) non polar - non polar
§2. Hydrogen bond

■ Electromagnetic interaction

– the source of all intermolecular interactions which determine the properties of solids/liquids/gases
– the behaviour of particles in solution, chemical reaction and organization of biological structure

■ Gravitational interaction

– between atoms and molecules as well as elementary particles

– Ȧ to ∞
– tidal motion
– cosmological phenomena

Gravitational and intermolecular forces they determine maximum size that an animals or tree can
attain, the height that a liquid will rise in capillaries
Effect of medium

– screening of field
– Hydrophobic environment
– Hydrophilic environment
PH60206 by A. N. Gupta Lecture # 7, # 8, & # 9 7

Chemical bond formation

(all of you know)

§1. The chemical force which keep the atoms in any molecule together: Covalent, Ionic, Metallic, Reso-
nance
§2. Hybridization: mixing of the atomic orbitals to form new hybrid orbitals

■ one kind of hybrid orbitals have equal energy, identical shape and symmetrically orientation
■ Quantum mechanics focus on wave nature of electron
■ σ bonding: two atomic orbitals overlap end to end (head on)to form two σ molecular orbitals
■ σ bonding orbital: have lower potential energy than the bonding atomic orbital
■ σ ∗ antibonding orbital: have higher potential energy than the bonding atomic orbital
■ low electron density leaves only repulsion between nuclei
■ high electron density provide stability
■ So, number of molecular orbitals formed is always equal to the number of atomic orbitals com-
bined/mixed

§3. Assign electrons to molecular orbitals using

■ aufbau principle
■ Pauli exclusion principle
(a) no two identical fermions (half integral spin) can occupy the same quantum state
(b) total wave function for two identical fermions must be antisymmetric
■ Hund’s rule
(a) maximum multiplicity has lowest energy; maximum multiplicity is 2S + 1; S is total spin.
So, lowest energy for maximum S.
(b) for a given multiplicity, L should be lowest
(c) half filled or less filled, the molecular orbital (lowest J) has lowest energy

§4. π bonding: Two atomic orbitals overlap from side by side position along the internuclear axis to form
bonding and anti-bonding molecular orbitals. The electron density is located above and below the
inter nuclear axis.

Bond order
1
■ [ no. of electrons in bonding molecular orbitals - no. of electrons in antibonding molecular orbitals]
2
■ BO used to predict the relative stability of any molecules

■ Zero or -ve value means the bond has no stability

■ Examples for BO calculations and comments

PH60206 by A. N. Gupta Lecture # 7, # 8, & # 9 8

Applications
§1. Study interactions among biomacromolecules (polymers), it lead to self-assemble into an specific func-
tional three-dimensional structure.

§2. A polymer, however, can actually bend like a string! There are more consequences. Perpendicular to
the strong (covalent) forces along the one-dimensional backbone, weaker forces may come into play;
forces that would be insignificant if the atoms were not brought together by the backbone bonds. But
given that the backbone forces these monomers together, the cooperative binding of many of these
weaker forces, both within the same molecule and between different molecules.

§3. stability of molecules

§4. Interaction potential and second virial coefficient

§5. Biophysics is kB T-Physics. The relevant energy scale for the molecular interactions that control all
biological mechanisms in the cell is kB T, This is not true for most of the systems described in a typical
physics curriculum, for example:

(a) the hydrogen atom, with an energy scale ∼ 10 eV, whereas kB T is 1/40 eV;
(b) binding energies of atoms in metals; covalent bonds: energy ∼ 1 eV;
(c) macroscopic objects (pendulum, billiard ball), where even a 1 mg object moving with a speed of
1 cm/s has an energy ∼ 109 eV.

The approach is therefore different. For example, in the solid state one starts with a given structure
and calculates energy levels. Thermal energy may be relevant to kick carriers in the conduction band,
but kB T is not on the brink of destroying the ordered structure.
Soft-matter systems often self-assemble in a variety of structures (e.g. amphiphilic molecules in water
form micelles, bilayers, vesicles, etc.; polypeptide chains fold to form globular proteins). These ordered
structures exist in a fight against the disruptive effect of thermal motion. The quantity that describes
the disruptive effect of thermal motion is the entropy S, a measure of microscopic disorder. So for
these systems energy and entropy are both equally important, and one generally considers a free energy
F=A=E-T S.

§6. Proteins are polypeptides, or random polymers made up of amino acid monomers.

§7. Chemical details are everything. Ultimately, no two proteins are alike. A ‘point mutation’ changing
one ‘residue’ (= amino acid) in a 100-residue protein can make the difference between life and death.

§8. complex fluids possess features that are independent of chemical details. All colloids undergo Brownian
motion. Polymers of all kinds share features arising out of intramolecular connectivity. Aspects of
the self-assembly of any surfactant (or surface-active molecule) can be understood by treating it as a
truncated cone of suitable shape.

§9. Recent trends: Forces between atoms and molecules in gases(using quantum and statistical calcula-
tions) for physical properties; Chemical bonding ( atoms/molecules in solids); long range interaction
between surface and molecules; Static (equilibrium, time-independent) and dynamic (non-equilibrium,
time-evolving) systems.
PH60206 by A. N. Gupta Lecture # 7, # 8, & # 9 9

Consider a molecule in the gas phase and Let the attractive pair potential be
C
u(r) = − ; where n is an integer
rn
Let consider a system (region of space, solid, liquid/gas or outer space) having number density ρ

The number of molecules in a given region of space r and r + dr is ρ 4 πr2 dr

Total interaction of one molecule with all the other molecule in system
Z L   σ (n−3) 
2 4π Cρ 4πCρ
U (r) = u(r)ρ4 π r dr = − (n−3)
1− =− for n > 3 and L >> σ
σ (n − 3)σ L (n − 3) σ (n−3)
where σ is hard sphere diameter of the molecule, L is the size of the system.

■ since σ < L, the larger distance contributions to the interaction will disappear only for values of n > 3

■ If n < 3, it means the second term contribution can not be ignored. The contribution from more distant
molecule will dominate over that of nearby molecules. So, size of the system matters, n=1 for gravi-
tational interaction. The distant planets, stars, and galaxies are strongly interacting with one another.

■ Hence the bulk properties of solid/ liquid/ gas do not depends on the volume of material or on the
size of the container, but only on the forces between them.

Real gas equation

a
(P + ) (V − b) = R T ; where b is account for finite volume/size of the molecules;
V2
a/V 2 extra pressure by attractive intermolecular forces (van der Waal force)

The pair potential is given by

−A B
u(r) = n + m
r r
For L-J potential:
n=6 and m=12,
A = 10−77 J m6 ;
B = 10−134 J m12
PH60206 by A. N. Gupta Lecture # 7, # 8, & # 9 10

Derive van der Waal equation of state from interaction potential

Workout problem in the class:
−C
Hint: let potential be u(r) =
rn
use chemical potential (µ) and concentration (X1 and X2 ) in any two region at equilibrium.

X1 = X2 exp −(µi1 − µi2 )/kT ; where i is type of molecule and numbers are regions. If there are many

different regions (phases/states) in a system each with different energies µin but at the same P and T, then
condition of equilibrium is:
µi1 + kT ln(X1 ) = µi2 + kT ln(X2 )..

µin + kB T ln(Xn ) =Constant (say µ); for all n=1,2,3,...

Z ∞
4πCρ
µin = u(r) ρ 4 π r2 dr = − = −A ρ ;
σ (n − 3) σ (n−3)
2π C
where ρ is specific density, and A/2 =
(n − 3)σ (n−3)
For molecule of finite size,
1 4 π σ3
X2 = ; Use v = 1/ρ, and B = is excluded volume interaction. So
(v − B) 3
ρ
⇒ X2 =
1−B ρ
ρ
µ = −A ρ + kB T ln
1−B ρ
Use thermodynamic relation between P and µ (consider Gibbs free energy and change in variables)
     
∂µ ∂P ∂µ
= v = 1/ρ, or, = ρ
∂P T ∂ρ T ∂ρ
Find P, using
Z ρ  
∂µ kB T −A/2 kB T −B
P = ρ dρ = −A/2 ρ2 − ln(1−B ρ) = 2
+ ; ∵ ln(1−Bρ) ∼ .
0  ∂ρ T B  v (v − B/2) (v − B/2)
n2
  
−A/2 kB T V
P+ 2
= ⇒ P + a 2
− b = n R T.
v (v − B/2) v n
A B
Here, a = , & b = , attractive and repulsive contributions, respectively.
2 2
Questions:

§1. Derive the gravitational pressure P0 at the center of a liquid sphere (Liquid sphere has radius R and
2π
uniform density ρ). Ans: G ρ2 R 2
3
§2. Estimate the radius R of a water sphere for which the gravitational pressure at the centre would be,
P0 = 1 atm. Ans: R= 28 km.

Comments from Students: