PH2070: Jan ~ May 2021: End Semester Examination Duration: 150 minutes Suppose that a set of reactions forms a loop, as shown in the Figure ay applying the law of mass action, one can proceed to find the steady-state concentrations of A,B and C. However, thermodynamic cequilarium requices thatthe free energy of each state be the same s0 that each individual reaction isin equilibrium. In other words, at equlisrium there is not only, say, no net change in (8, thereis also ‘no net conversion of B to Cor B to A. a) Can al the rate constants be Independent? b) ifthe answer to (a) is a‘No’, provide reasons and determine the relationships between the various rate constants. If the answer to (a) an ‘Yes’, provide reasons. (c) Consider the reaction involving only two species A and B. Indicate the relationship between the rate constants and the thermodynamic free energies involved. (4) Suppose the equilibrium constant associated with the reaction involving A and B is given to be 10 at T= 300 K, Estimate the changes in chemical potential and entropy. (6) Suppose the change in enthalpy s 10 kcal/mol at T= 300K, what would be the equilibrium constant at T=310 K? Take the reactions to bein the gas phase for parts (d) and (e). [8 Marks} Consider the formation of a polymer from monomers as a ‘chemical reaction’ whose equilibrium can be described by the following expression: Po +P Prat (a) Express Kaas a function ofthe concentrations ofthe ‘reactants’ and ‘products! (b) Setn= 1 in the expression obtained in (a) to get [a] in terms of [Pi], the monomer concentration. Proceed iteratively for n = 2,3. and get the general expression fr [Pa] in terms of monomer concentration. Rewriteit using « = ~Ini(Pi]/Kg) Comment on the behaviour of [Px] when [Ps] < Ke (4) Obtain the average length ofthe polymer (n), Sketch the average len monomer concentration. [8 Marks] as a function of the In one dimension, the governing equation for p(x, £), the probability density of finding a particle at position x at time tis given by a). Obtain the general solution for p(x, t) under steady state conditions. ©) Determine the unknowns using the conditions that (i) the probability of finding the particle ‘anywhere in the interval (0,4) is equal to 1, and (i) the probability vanishes when the particle reaches d. In other words, when the particle disappears at x = 4, it reappears at x = Oto ensure that the first condition is satisfied, ©) Obtain an expression for the probability current density. d) What is the time that a particle would take to reach 6 ? [Hint: Note the dimensions of the probability current density that was obtained in (c]. [Note: This time that it takes to reach the position 6 for the first time is called the mean first passage time - averaged over many trajectories]. (8 Marks}4, Modeling polymerization in terms of rate equations: The time evolution ofthe robabiltydstribution's Oba a governed by four distinct asses of process ands Si vie captured mathematically as oe e Se KanPn-aPi + _KoPnst _~_KonPabt — koe? dt Adationto Fy femoval fom Raut addtionto Py removal fom Py If ais the length of a monomer, we can write the total average length of the filament as => naPp a) Write down the expression for the time derivative of (L). 'b) Obtain a simplified expression in terms of P:, a, kei and ker, using the following identity repeatedly: yn, €) One useful way to visualize the significance of this result is to plot the rate of growth as a function of monomer concentration. Show that, depending upon the concentration, the filaments will either grow or shrink. Identify the critical concentration for which there is neither growth nor decay of the filament. [ 10 Marks) 5. We had discussed in the class the outcome when the bundled flagella of the E.Coli executes a counter-clockwise rotation in a ‘rigid’ manner within a viscous fluid as depicted in the figure here. (2) Obtain an expression for the force with which the organism propels to the left as shown in the figure, (0) Deduce an expression for the speed with which the organism would ‘run’ (c} Is low-Reynolds number regime necessary for your analysis? Explain. Take the viscosity of the medium to be pi. Proceed by recognizing that every short ‘rod’-Iike segment of the ‘rigid’ rotating helix experiences distinct drag forces parallel and perpendicular to the axis of the ‘rod’. This in turn arises from the distinct drag coefficients associated with the motion of the ‘rod-like segment parallel to the fluid flow and perpendicular to the fluid flow. [8 Marks} 6. Consider a bacterium, idealized as a sphere of radius 1 yum, propelling itself at 1 m/s in water. At time zero the bacterium suddenly stops swimming and comes toa stop, following Newton’s Law of motion with the Stokes drag force Take the density and viscosity of water to be 10° kg/m? and 10° kg/{m-s) and respectively 2, How far does it travel befor it stops? Comment on the result. '. Our discussion of Brownian motion assumed that each random step was independent of the previous one; thus, for example, we neglected the possibility ofa residual drift speed left over from the previous step. In the light of (a), would you say that this assumption is justified for a bacterium? (6 Marks]10. (2) Using the given circuit diagram, obtain an expression for the membrane potential Vw in terms ofthe circuit elements. Ris the membrane resistance tothe flow of Na" ions. Reis finite when the Sodium channel is open, and infinite when the Socium channel is closed. Vand Via are the Nernst potentials for K* and Na’ ions respectively. isthe resting permeability ofthe cell membrane tothe flow of ions 1 {b) Suppose Ris is given by pe/A, where ps is the resistivity of the oursise Vo vorte resting membrane in ohms-m? and As the surface area of the cell. Assuming a spherical cell, obtain an expression forthe cell diameter from the result got in (a) () What are the constraints on Vi Vin, and Vi ifthe cell diameter has to be > 0? (4) Estimate the cell diameter for a membrane potential of —40 mi given Rc is 4x 10°° ohms, Vc=—60 mV, Vps= 60 mV and pe= 11 ohms mn’ (6) What are upper or lower bounds on Vy, if any, due to thermal voltage fluctuations? Take the temperature to be 27°C. (0 From (0), i looks ike the cell diameter can be made smaller by making the membrane more leaky tok" ions. Butas the cell diameter keeps reducing, comment on the implications in terms of the geometry, the Nernst potentials, and the operation of the sodium/potassium pump. {10 Marks} Consider 100 mmol/L each of K"and Cl ions in the extracellular region. Consider 100 mmol/L teach of k and Pr-ions to be present in the intracellular region. Note that electroneutrality is maintained in each region. (a) Given that the membrane separating these regions is not permeable to Pr'ions but is permeable to K” and Cr-ions, examine qualitatively the nature of equilibrium in terms of chemical potentials and electrochemical potentials. (b) Would osmosis occur? { 8 Marks] Consider a particle, A, undergoing one dimensional diffusive motion with a diffusion coefficient D. (a) Obtain an expression for the time derivative of the mean square displacement and comment on the ‘speed’ of the diffusing particle. Examine it as ¢ -» 0 and explain if anything is, wrong about the outcome. (b) Consider another identical particle, 8, moving with uniform speed up. Sketch the mean square displacement as a function of time for both these particles and identify a characteristic time, iFit exists. c) Comment on the ‘speed’ of the diffusing particle in the context of uo. (d) Take D as 10% m/s and us as 10 body lengths/s and examine the results (2}~(c) for E.Coli which is about 2 jm long. (8 Marks) Find the value n = that causes the function ™ w W tobe ata maximum, for constants p and N. (1 =a pL ep) Use Stirling's nl(N =n)! spprotmaton: 2 = (t/e). (amasrt 2. (a) Noel lons sometimes cross a biological membrane in one direction but | not the other. Figure shows how the application of an external volt 1ge opens a protein channel to allow ions to pass through, Consider a simple model for voltage-gated ion conductance, Based on the assumption thatthe applied field orients a dipole a within the protein channel. (a) Write down a general expression for the ratio ofthe probabilities that the channel sin the open or) Apliet kt closed states in terms of AG, the free energy required to open the channel in the absence of the applied field, and w, the work eo performed by the applied electrostatic field in orienting the 0 6 dipole. (b) Express w in terms of the product of the applied \ potential and an effective charge qr (this will be in terms of the ° actual charge and other geometrical parameters — see figure). y (c) Find the fraction of time that the channel is open in terms of o = your answer for (a). Note that the ion flow through the channel is Ao proportional to this fraction. (d) Sketch the result obtained in (c) oe asa function of applied potential and comment on the features. = (€} Sketch the effect of changing the temperature (overlay in ())- (10 Marks} In biological systems, itis often required to bind two (or more) ligands to make the reaction proceed. We can madel this process by postulating a receptor Rwhich likes to (ddl «hdl bind two ligands but penalizes with high [ower] [Es | [es] energy the binding of single ligands There are Ny sites in total and N, ligands. a) No bound ligands: Energy is given by Ey = N,#s. What is the multiplicity W, ? ®) Two bound ligands: Energy is given by Ea» = (N, — 2)é5 + 2ep. Whats the licity Wz»? (Single site occupancy of ligand is ruled out) ). What is the probability pp of finding the double receptor bound to two ligands? Express your answer in terms of the ligand concentration c, = N,/Ny and the positive energy change A = €5 — Ep. This result describes the cooperative binding effects seen for hemoglobin. d) Compare your result in (c) with what you would get if only single occupancy of the ligand is considered (Double occupancy i ruled out). Note that you have to work out W, and pp. e) Comment on the rate at which p, and p2, change with c;. In particular, check for any inflection in these probabilities. Not Sc, S 1. [10 Marks} ish JF