Lec 1 This lecture discusses various topics
related to biology from a
physics/engineering/quantitative science
perspective. It emphasises the importance
of measurement, quantification, and models
in understanding living systems. The lecture
also highlights the need to apply principles
from physics, engineering, and mathematics
to explain biological processes. It mentions
the concept of thermal energy and its
effects on living beings, as well as the
significance of temperature in relation to
average kinetic energy. The document
touches on topics such as DNA melting,
protein denaturation, and diffusion. It also
mentions the interplay of structure and
information in biology, randomness in life
processes, and the prediction of biological
phenomena. Additionally, it discusses the
motion and force in biology, pattern
formation, and the implications of random
movements on biomolecules.
Ways to perturb objects-
1. Temperature
2. Pressure/force
3. Volume
4. Concentration
Temperature≡<kinetic energy>
2
𝑚<𝑣 >
𝑇= 3𝑘
,k=boltzmann constant
Randomly jiggling water molecules kick
other bigger molecules (proteins in water),
causing thermal fluctuation≡brownian
motion.Typical energy of these “kicks” is
“Thermal energy”.𝐸 ≈ 𝑘𝑇
This energy can destabilise bonds, DNA
melting and protein denaturation.DNA from
nucleosomes (DNA wrapped around histone
proteins) can partially unwrap due to
thermal fluctuations.
Distance a protein of size(radius= a nm) can
diffuse-
𝑘𝑇
𝑟 = 6𝐷𝑡 where t=time and 𝐷 = 6πη𝑎
Lec 2 This lecture discusses the laws of
physics and chemistry that govern life at a
molecular level. It explains the role of
thermal energy and the probabilistic nature
of biological processes. Additionally, it
delves into the concept of protein folding
and the preferred conformations of proteins.
It also emphasises that systems can exist in
various states with different probabilities,
even if they are not in their minimum energy
state. Lastly, it mentions the equation of
motion and the relationship between force
and acceleration in our observed world.The
impact of thermal energy on biological
processes at a molecular level is that it
introduces randomness and uncertainty.
With thermal energy, a cell or biomolecule
falling in a test tube under an external force
can be found anywhere due to thermal
kicks. This means that the location of the
cell or biomolecule cannot be certain and
we have to use probability ideas. The
thermal energy also contributes to the
stochastic nature of biology, making it
probabilistic.Boltzmann probability-
−
𝐸(𝑧)
𝑘𝑇
𝑃(𝑧) = 𝐴𝑒
Protein folding is of great significance in
biological systems. Proteins are essential
molecules that perform a wide range of
functions in living organisms. The unique
three-dimensional shape of a protein, which
is determined by its folding, is crucial for its
proper functioning. The folded structure
allows proteins to interact with other
molecules, such as enzymes, receptors,
and DNA, and carry out specific biological
processes.The folding process is highly
complex and precise. Proteins are initially
synthesised as linear chains of amino acids,
and they must fold into their correct shape
to be functional. Improper folding can lead
to protein misfolding and aggregation, which
are associated with various diseases,
including neurodegenerative disorders like ● Other interaction energies: How
Alzheimer's and Parkinson's.Understanding other factors such as Lennard-Jones
protein folding is essential for unravelling energy, curvature, and twist affect
the mechanisms of protein function and the intermolecular effective potential
disease. Researchers study protein folding in biology.
to gain insights into how proteins adopt their ● Bio-filaments properties: How the
native structures and how they can be elasticity, bendability, and rigidity of
manipulated or targeted for therapeutic bio-filaments like actin or DNA can
purposes. By understanding the principles be inferred from their microscopic
of protein folding, scientists can design images. Thermal fluctuations can
drugs that specifically target misfolded make them bend and affect their
proteins and develop strategies to prevent force generation.
or treat protein misfolding diseases. ∂𝐶
Diffusion flow, 𝐽𝑑 =− 𝐷 𝑥
Overall, protein folding plays a critical role in ∂𝑥
the proper functioning of biological systems Drift flow,
and has significant implications for both 𝑓 𝑐𝑞 ∂𝑉
basic research and medical applications. 𝐽𝑒 = 𝑐𝑣 = 𝑐 6πη𝑎
= 6πη𝑎 ∂𝑥
Probability of finding protein in conformation At equilibrium, drift=diffusion,solving
−
𝐸(𝑛)
𝐸(𝑛) 𝑘𝑇 𝐶1(𝑒𝑞)
𝑒 𝑘𝑇 − 𝑘𝑇
differential gives,∆𝑉 = 𝑙𝑛
𝑞 𝐶2(𝑒𝑞))
𝑃(𝑛) = 𝑍
,𝑍 = ∑ 𝑒
This is the nernst equation and it gives
𝑛
ΔV=resting potential.
For the parameters relevant to molecular
Computing screened potential gives,
biology, inertial force contribution is
𝑟
negligible compared to viscous force. So at 𝐵 − λ ϵ𝑘𝑇
low reynolds number, force∝velocity. 𝑉= 𝑟
𝑒 ,λ =
2
𝐴∑𝑞
Lec 3 This lecture talks about- 𝑖

● Electrostatic potential difference: 𝜆= debye length≈ 1nm

How ion channels across cell
membranes create a voltage
difference that is essential for nerve
signals and neurons. The Nernst
equation gives the potential
difference at equilibrium, also known
as the resting potential.
● Screened electrostatic potential:
How the presence of ions in salty
water reduces the effective
interaction between charged
macromolecules like DNA and
proteins. The screened Coulomb
potential falls exponentially with
distance and is negligible beyond 1
nm.
Lennard Jones energy -
σ 12 σ 6
VLJ(r)=4ϵ⎡( 𝑟 ) − (𝑟) ⎤
⎣ ⎦
Lec 4 This lecture talks about-
● Entropy and life: The lecture explores
the concept of entropy and how it
relates to life. Entropy is a measure of
disorder or randomness in a system. It
also connects to information theory,
which quantifies the amount of
information in a message or a
sequence. Entropy is relevant for
understanding biological systems,
 such as DNA, proteins, and cells, and
how they evolve and communicate.
● Free energy and equilibrium: The Lec 5 In this lecture-
lecture explains how free energy is the
● Free energy landscape: A concept that
energy available to do work in a
describes the possible states and
system, and how it depends on both
transitions of biomolecules in terms of
the internal energy and the entropy of
energy and entropy. The landscape
the system. Free energy is minimised
has hills and valleys that represent the
when a system reaches
stability and rate of biological events,
thermodynamic equilibrium, which
such as protein folding and chemical
means there is no net change in the
reactions.
system. However, living systems are
● Protein folding: A process by which a
constantly out of equilibrium, as they
linear sequence of amino acids folds
take in and use energy from their
into a three-dimensional structure that
environment. Equilibrium is equivalent
determines its function. The folding is
to death for living systems.
guided by a funnel-like free energy
● Examples and calculations: The
landscape that has a global minimum
lecture provides some examples and
corresponding to the native
calculations to illustrate the concepts
configuration of the protein.
of entropy and free energy. For
● Chemical reactions: A process in
instance, it shows how to calculate the
which molecules change their
entropy of protein arrangements on
structure and composition by breaking
DNA, and how to calculate the free
and forming bonds. The free energy
energy of binding between proteins
landscape shows the difference in free
and DNA. It also shows how to
energy between the reactants and
calculate the entropy of DNA
products, and the activation energy
sequences across different species,
required to overcome the transition
and how to use it to estimate the
state. Enzymes can lower the
evolutionary conservation or diversity
activation energy and speed up the
of a gene or a protein.
reaction rate, but do not change the
Entropy, S=− 𝑘Σ𝑃(𝑖)𝑙𝑛𝑃(𝑖),
equilibrium.
P(i)≡probability of ith arrangement ● Differentiation of cells: A process by
Method for calculating- which cells acquire specialised
functions and characteristics by
expressing different genes. The
differentiation can be modelled as a
movement in a complex free energy
landscape, called the epigenetic
landscape, that has multiple valleys
corresponding to different cell types.

Lec 6 In this lecture-
● Chemical energy to mechanical
energy: How to convert the free
energy of a chemical reaction to
mechanical work, such as force or
motion. The lecture uses the example
of actin polymerization and
depolymerization, which can push or
pull objects in cells.
● Actin transducer: A molecular
machine that uses actin monomers
and filaments to generate force and
movement. The lecture explains how
actin monomers bind to ATP and form
filaments, and how ATP hydrolysis
changes the structure and state of
actin, breaking the symmetry and
creating a direction for motion.
● Treadmilling and force generation: A
phenomenon where actin filaments
grow at one end and shrink at the
other, resulting in a net movement of
the filament. The lecture shows how
to calculate the polymerization and
depolymerization rates, the critical
concentration, and the maximum
force that actin can generate under
different conditions.
● Microtubules and bending: Another
type of filament that can convert
chemical energy to mechanical
energy. The lecture briefly mentions
how microtubules use energy to bend
and how bending and dynamics can
pull a ring.
Lec 7 In this lecture-
● Microtubule dynamics: Microtubules
are cylindrical polymers composed of
tubulin dimers that can switch
between phases of growth and
shrinkage. This behaviour is called
dynamic instability and is powered by
GTP hydrolysis.GTP-tubulin cap: The
growing end of a microtubule has a
stabilising cap of GTP-tubulin subunits
that prevent depolymerization. The
size of the cap depends on the
mechanism and rate of GTP
hydrolysis, which is stimulated by
polymerization. The cap can be small
or fluctuating, depending on the
model.
● Experimental evidence: Various
experiments have shown that GTP
hydrolysis is necessary for dynamic
instability, such as using GMPCPP, a
non-hydrolyzable form of GTP, or
diluting the tubulin concentration.
Other experiments have used laser
cutting or optical tweezers to measure
the cap size and fluctuations.
● Regulatory proteins: In cells,
microtubule dynamics are modulated
by many microtubule-associated
proteins (MAPs), such as
polymerases, depolymerases, and
plus-end-tracking proteins (þTIPs).
These proteins affect the growth rate,
catastrophe frequency, and rescue
frequency of microtubules.
● The role of GTP hydrolysis in
microtubule dynamics: GTP hydrolysis
is necessary for the switching
behaviour of microtubules between
growth and shrinkage. It also affects
the stability of the microtubule lattice
and the size of the GTP cap at the plus
end.
● The mechanisms of GTP hydrolysis Lec 8 In this lecture-
stimulation: GTP hydrolysis can be
● Molecular machines: Different types
stimulated by different types of
of machines that make the cell
interactions between neighbouring
function, such as motors, cilia, flagella,
tubulin dimers in the polymer. One
replication machinery, and translation
possible mechanism is the “coupled”
machinery. These machines are made
hydrolysis, where incoming dimers
of proteins, filaments, and chemical
trigger the hydrolysis of the terminal
gradients.
dimers. Another possibility is the
● Examples of molecular machines: The
lattice incorporation, where GTP
lecture gives some examples of how
dimers have more neighbours after
molecular machines work, such as
being fully integrated into the lattice.
kinesin and dynein that move along
● The fluctuations in microtubule
microtubules, myosin that pushes
growth: Recent experiments using
actin, F0-F1 motor that makes ATP,
optical tweezers observed rapid
DNA helicase that separates DNA
shortening excursions of microtubule
strands, and ribosome that makes
growth without catastrophe. This
protein from mRNA.
suggests that either the GTP cap is
● Regulation of molecular machines:
longer than previously thought, or that
The lecture also explains how
the individual protofilaments have
molecular machines can be switched
different lengths and the tube
on and off by reorganising proteins on
structure provides stabilisation.
DNA, such as histones, transcription
● Dynein: A motor protein that binds to
factors, and binding protein. These
microtubules and moves towards the
processes require ATP-dependent
minus end. Dynein is involved in
sliding and disassembly of protein
transporting cargo, such as
complexes.
chromosomes, inside the cell.
● Evolution of molecular machines: The
● Chameleon colour change: An
lecture ends with a question of how
example of how dynein and kinesin
evolution can produce such complex
can control the spatial organisation of
machines. It suggests that natural
molecules. Chameleons change
selection is a powerful force that can
colour by moving pigment granules
create functional structures from
inside their skin cells. These granules
random variations.
are carried by dynein and kinesin
along microtubules.
● Myosin: Another motor protein family
that binds to actin, a different type of Lec 9 In this lecture-
cytoskeletal filament. Myosin uses
● Evolution and complexity: How natural
ATP hydrolysis to push actin and
selection can produce complex
generate force. Myosin and actin are
machines like cells and organisms in a
responsible for muscle contraction
finite time, using a simple algorithm
and movement.
that mimics evolution. The algorithm
involves random mutations,
 comparisons with a target sentence,
and selection of the fittest characters.
● Diversity and statistics: How evolution
generates diversity in a population,
using a simple model called the
Wright-Fisher model. The model
shows how the frequency of alleles
changes over generations due to
random sampling and mutations. The
model uses ideas from statistics such
as binomial distribution and
probability.
● Genetic algorithm: How the power of
natural selection inspires a computer
science technique called genetic
algorithm, which is widely used today.
The technique uses evolution-like
steps such as mutation,
recombination, and selection to find
optimal solutions to complex
problems.
Lec 10 In this lecture-
● Quantum detection of light: The
lecture explores the question of
whether human eyes can detect single
photons, which are quantum particles
of light. It also discusses the
implications of quantum mechanics
for the nature of light and its
interference patterns.
● Biology and engineering of vision:
The document explains how the eye
works, especially the rod cells that are
sensitive to low light.Rhodopsin
undergoes conformational change
when a photon falls on it, converting
light energy to chemical potential
Conformational change of rhodopsin
leads to a series of chemical reactions
leading to ion-channel
opening/closing and voltage
difference.Cones detect light when
intensity is high,they detect colour.
● Statistics and data analysis: The
document introduces the Poisson
distribution, which is a mathematical
model for describing random events,
such as photons or mangoes falling. It
also shows how to use the Poisson
distribution to fit experimental data
and estimate the number of photons
needed to trigger vision.
where M=αI, M is average number of
particles and I is intensity.
Lec 11 In this lecture-
● Predicting the future: The goal is to
forecast the state of a system after a
certain time or at equilibrium, when
the forces or flows balance. The role
of temperature and potential energy is
discussed.
● Modelling the dynamics: The
equations that describe how a system
changes with time are presented. For
systems without temperature,
Newton’s equations are used. For
systems with temperature, Langevin
 equation or diffusion equation are At steady state,pattern is independent
used. of time,
● Langevin equation-
2 𝑥
∂ [𝐵] − 𝑙
𝑑𝑣 = 𝑘[𝐵] ⇒ [𝐵] = β𝑒
𝑚 𝑑𝑡
=− α𝑣 + 𝑓 + 𝑓(𝑇) ∂𝑥
2

where <f(T)> =0, Var(f(T)) ∝ T where 𝑙 = 𝐷/𝑘

● Effect of thermal fluctuations: The Reactions based on the threshold of
random force that arises from concentration leads to patterns.
temperature is introduced and its
properties are explained. The ● Brain structure and function: The
Boltzmann distribution is used to lecture briefly introduces the brain as
describe the probability of states at a network of neurons, which
equilibrium. communicate through electrical and
chemical signals. It mentions that
memory storage is related to the
Lec 12 In this lecture- connection between neurons, and that
the brain has different parts that
● Patterns in nature: The lecture perform different functions.
explores how patterns emerge in
natural phenomena, such as the
formation of the head-tail axis in fruit
flies, or the structure of the brain. It
discusses the role of reaction
diffusion processes, which involve the
production, movement, and
degradation of chemical substances,
in creating patterns with a
characteristic length scale.
● Reaction diffusion equation: The
lecture presents a simple equation
that describes the change in
concentration of a substance over
time and space, depending on its
diffusion constant, degradation rate,
and initial condition. It shows how the
equation can be solved to obtain an
exponential decay function, which
gives the length scale of the pattern.
2
∂[𝐵] ∂ [𝐵]
∂𝑡
= 𝐷 2 − 𝑘[𝐵]
∂𝑡

where k is the degradation constant.