Lec 1 This lecture discusses various topics Lec 2 This lecture discusses the laws of
related to biology from a physics and chemistry that govern life at a
physics/engineering/quantitative science molecular level. It explains the role of perspective. It emphasises the importance thermal energy and the probabilistic nature of measurement, quantification, and models of biological processes. Additionally, it in understanding living systems. The lecture delves into the concept of protein folding also highlights the need to apply principles and the preferred conformations of proteins. from physics, engineering, and mathematics It also emphasises that systems can exist in to explain biological processes. It mentions various states with different probabilities, the concept of thermal energy and its even if they are not in their minimum energy effects on living beings, as well as the state. Lastly, it mentions the equation of significance of temperature in relation to motion and the relationship between force average kinetic energy. The document and acceleration in our observed world.The touches on topics such as DNA melting, impact of thermal energy on biological protein denaturation, and diffusion. It also processes at a molecular level is that it mentions the interplay of structure and introduces randomness and uncertainty. information in biology, randomness in life With thermal energy, a cell or biomolecule processes, and the prediction of biological falling in a test tube under an external force phenomena. Additionally, it discusses the can be found anywhere due to thermal motion and force in biology, pattern kicks. This means that the location of the formation, and the implications of random cell or biomolecule cannot be certain and movements on biomolecules. we have to use probability ideas. The Ways to perturb objects- thermal energy also contributes to the 1. Temperature stochastic nature of biology, making it 2. Pressure/force probabilistic.Boltzmann probability- 3. Volume − 𝐸(𝑧) 𝑘𝑇 4. Concentration 𝑃(𝑧) = 𝐴𝑒 Temperature≡<kinetic energy> Protein folding is of great significance in 2 𝑚<𝑣 > biological systems. Proteins are essential 𝑇= 3𝑘 ,k=boltzmann constant molecules that perform a wide range of Randomly jiggling water molecules kick functions in living organisms. The unique other bigger molecules (proteins in water), three-dimensional shape of a protein, which causing thermal fluctuation≡brownian is determined by its folding, is crucial for its motion.Typical energy of these “kicks” is proper functioning. The folded structure allows proteins to interact with other “Thermal energy”.𝐸 ≈ 𝑘𝑇 molecules, such as enzymes, receptors, This energy can destabilise bonds, DNA and DNA, and carry out specific biological melting and protein denaturation.DNA from processes.The folding process is highly nucleosomes (DNA wrapped around histone complex and precise. Proteins are initially proteins) can partially unwrap due to synthesised as linear chains of amino acids, thermal fluctuations. and they must fold into their correct shape Distance a protein of size(radius= a nm) can to be functional. Improper folding can lead diffuse- to protein misfolding and aggregation, which 𝑘𝑇 𝑟 = 6𝐷𝑡 where t=time and 𝐷 = 6πη𝑎 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
How ion channels across cell Lennard Jones energy - membranes create a voltage σ 12 σ 6 difference that is essential for nerve VLJ(r)=4ϵ⎡( 𝑟 ) − (𝑟) ⎤ ⎣ ⎦ signals and neurons. The Nernst equation gives the potential difference at equilibrium, also known Lec 4 This lecture talks about- as the resting potential. ● Entropy and life: The lecture explores ● Screened electrostatic potential: the concept of entropy and how it How the presence of ions in salty relates to life. Entropy is a measure of water reduces the effective disorder or randomness in a system. It interaction between charged also connects to information theory, macromolecules like DNA and which quantifies the amount of proteins. The screened Coulomb information in a message or a potential falls exponentially with sequence. Entropy is relevant for distance and is negligible beyond 1 understanding biological systems, nm. 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 7 In this lecture-
Lec 6 In this lecture- ● Microtubule dynamics: Microtubules
are cylindrical polymers composed of ● Chemical energy to mechanical tubulin dimers that can switch energy: How to convert the free between phases of growth and energy of a chemical reaction to shrinkage. This behaviour is called mechanical work, such as force or dynamic instability and is powered by motion. The lecture uses the example GTP hydrolysis.GTP-tubulin cap: The of actin polymerization and growing end of a microtubule has a depolymerization, which can push or stabilising cap of GTP-tubulin subunits pull objects in cells. that prevent depolymerization. The ● Actin transducer: A molecular size of the cap depends on the machine that uses actin monomers mechanism and rate of GTP and filaments to generate force and hydrolysis, which is stimulated by movement. The lecture explains how polymerization. The cap can be small actin monomers bind to ATP and form or fluctuating, depending on the filaments, and how ATP hydrolysis model. changes the structure and state of ● Experimental evidence: Various actin, breaking the symmetry and experiments have shown that GTP creating a direction for motion. hydrolysis is necessary for dynamic ● Treadmilling and force generation: A instability, such as using GMPCPP, a phenomenon where actin filaments non-hydrolyzable form of GTP, or grow at one end and shrink at the diluting the tubulin concentration. other, resulting in a net movement of Other experiments have used laser the filament. The lecture shows how cutting or optical tweezers to measure to calculate the polymerization and the cap size and fluctuations. depolymerization rates, the critical ● Regulatory proteins: In cells, concentration, and the maximum microtubule dynamics are modulated force that actin can generate under by many microtubule-associated different conditions. proteins (MAPs), such as ● Microtubules and bending: Another polymerases, depolymerases, and type of filament that can convert plus-end-tracking proteins (þTIPs). chemical energy to mechanical These proteins affect the growth rate, energy. The lecture briefly mentions catastrophe frequency, and rescue how microtubules use energy to bend frequency of microtubules. and how bending and dynamics can ● The role of GTP hydrolysis in pull a ring. 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, undergoes conformational change and selection of the fittest characters. when a photon falls on it, converting ● Diversity and statistics: How evolution light energy to chemical potential generates diversity in a population, Conformational change of rhodopsin using a simple model called the leads to a series of chemical reactions Wright-Fisher model. The model leading to ion-channel shows how the frequency of alleles opening/closing and voltage changes over generations due to difference.Cones detect light when random sampling and mutations. The intensity is high,they detect colour. model uses ideas from statistics such ● Statistics and data analysis: The as binomial distribution and document introduces the Poisson probability. 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.
● 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 where M=αI, M is average number of problems. particles and I is intensity.
Lec 10 In this lecture- Lec 11 In this lecture-
● Quantum detection of light: The ● Predicting the future: The goal is to
lecture explores the question of forecast the state of a system after a whether human eyes can detect single certain time or at equilibrium, when photons, which are quantum particles the forces or flows balance. The role of light. It also discusses the of temperature and potential energy is implications of quantum mechanics discussed. for the nature of light and its ● Modelling the dynamics: The interference patterns. equations that describe how a system ● Biology and engineering of vision: changes with time are presented. For The document explains how the eye systems without temperature, works, especially the rod cells that are Newton’s equations are used. For sensitive to low light.Rhodopsin 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