8.593J - Biological Physics Spring 2010

General Information and Course Administration:

Lectures

TR 1:00 - 2:30 pm in Room 2-105

Recitations

R01: W 1pm in Room 26-322

Homework

Homework assignments will be posted on the course web site on alternate Tuesdays starting Tuesday February 2. The student's solutions to the homework will be due in the Physics Drop Boxes located on the 3rd floor of Bldg 8 at the intersection of Bldg 16, on the Monday thirteen days later by 4:30 PM. The student name should be clearly written on the upper right hand corner of the homework. Graded homework will be returned to students at the Tuesday lecture one week following the hand in of the assignment. The correct solutions to the problems will be distributed on the website promptly following the return of the graded assignment. No late homework will be accepted without prior permission of the lecturer.

Textbooks and Reference Books

There is no textbook available which contains the course material which will be presented during the lectures. The lectures themselves will be the primary source of content of the course. In addition to the blackboard presentations, lectures in the form of typed notes will be presented to students each week. Listed below are reference books which may prove useful in providing background material, particularly for the biological material.

  • Molecular Cellular Biology, J. Darnel H. Lodish, D. Baltimore. Pub. by Scientific American Books (1986).
  • Biochemistry, D. Voet and J. Voet. Pub. by John Wiley and Son (1990).
  • Binding and Linkage: Functional Chemistry of Biological Molecules, J. Wyman and S. J. Gill. Pub. by University Science Books, Mill Valley CA (1990).
  • Mechanisms of Cooperativity and Allosteric Regulation in Proteins, M. Perutz. Pub. by Cambridge University Press (1990).
  • Human Physiology: The Mechanisms of Body Function, Vander, Sherman and Luciano. Pub. by McGraw-Hill (1980).
  • Allosteric Enzymes, Ed and G. Herve. Pub. by CRC Press (1989).
  • Human Hemoglobins, H. F. Bunn, B. Forset, and H. M. Ranney. Pub. by W. B. Saunders & Co. (1977).
  • Proteins: Structures and Molecular Properties, T. E. Creighton. Pub. by W. H. Freeman & Co. (1984).
  • Protein Condensation: Kinetic Pathways to Crystallization and Disease, J. D. Gunton, A. Shiryayev, and D. L. Pagan, Pub. by Cambridge University Press (2007).

Term Papers

Students will write a term paper in place of a final exam. The topic of the term paper should be a subject connected with, but an extension of, a subject presented in the course. Students should have selected the theme of the paper, with the agreement of the lecturer by April 16. The term paper must be handed in to the Physics Drop Boxes (3rd floor of bldg 8 at the corner of bldg16), by 5 pm Monday, May 10.

A list of publications which are useful leads for term paper topics is:

  1. How Enzymes Work: Analysis by Modern Rate Theory and Computer Simulations. M. Garcia-Viloca, J Gao, M. Karplus, and D. Truhlar. Science, Vol 303, 186-195, 2004 (9 Jan, 2004)
  2. Protein Folding and Misfolding. Christopher M. Dobson Nature Vol 426 884-890 2003 (18/25 2003)br />
  3. Mimicking Posttranslational Modifications of Proteins. Benjamin G. Davis Science Vol 303, 480-482 (23 January 2004)
  4. The Era of Pathway Quantification. Daniel E Koshland Jr. Science Vol 280, 852-853, 1998 (8 May 1998).
  5. Kinesin Walks Hand–Over–Hand. A. Yildiz, M, Tomishige, R.D. Vale, and P.R. Selvin. Science Vol. 303 676-679 (2004) 30 Jan 2004
  6. Mechanics of Motor Proteins and the Cytoskeleton by Jonathon Howard. Published by Sinauer Associates, Sunderland, MA 2001 ( ISBN 0-87893-334-4)
  7. BASR Domains Go On a Bender. M.C.S. Lee and R. Schekman Science Volume 303, pp 479-480 (2004)
  8. BAR Domains as Sensors of Membrane Curvature: The Amphiphysin BAR Structure. Peter et al Science Volume 303 pp 495-499 (2004)
  9. Synaptic Vesicle Endocytosis Impaired by Disruption of Dynamin-SH3 Domain Interactions. Shupliakov et. al. Science Vol 276 pp 259-263 (1997) (Note that references 7,8,9 all refer to the important topic of the mechanisms of endocytosis)
  10. Force-clamp Spectroscopy Monitors the Folding Trajectory of a Single Protein. J.M. Fernandez, and H.Li Science Vol 303 1674-1678 (2004) (12 March 2004)
  11. Allosteric Mechanisms of Signal Transduction. Jean-Pierre Changeux1 and Stuart J. Edelstein Science Vol. 308. no. 5727, pp. 1424 - 1428
  12. Robustness in simple biochemical networks. N. Barkai and S. Leibler Nature 387, 913 - 917 (1997)
  13. Chemosensing in Escherichia coli: Two regimes of two-state receptors. Juan E. Keymer, Robert G. Endres, Monica Skoge, Yigal Meir, and Ned S. Wingreen PNAS 2006 103: 1786-1791
  14. A feeling for the numbers in biology. R.Phillips and R. Milo, PNAS volume 106 pages 21465-21471 December 2009.
  15. Protein Condensation: Kinetic Pathways to Crystallization and Disease. J. D. Gunton, A. Shiryayev, and D. L. Pagan, Pub. by Cambridge University Press (2007).
  16. CO2mmon Sense. Wolf B. Frommer, Science, 327, 275-276 (2010)
  17. The Taste of Carbonation. J. Chandrasekhar et al. Science 326 443 (2009)

Grading

The final grade will be based on the performance in homework, and the grade on the term paper. Homework will contribute 60% and term paper 40% to the final grade.

Course Overview:

This interdisciplinary course has been developed under the auspices of the M.I.T. Department of Physics and the Harvard- M.I.T. Division of Health Sciences and Technology. It is addressed to seniors and graduate students in the Schools of Sciences, Engineering and the Division of Health Sciences and Technology who are interested in a detailed quantitative and analytic understanding of biological and physiological phenomena. In addition to the blackboard lecture presentations, students will be provided with typed notes on the topics covered.

The principal discipline which will underlie and unify the analysis in this course is statistical mechanics and thermodynamics. We shall provide at the first lecture a complete set of notes reviewing those elements of statistical mechanics and thermodynamics with emphasis on those most useful in applications to biological phenomena. In order to increase the time available for biophysical topics, we urge the student to read these notes on their own. When a particular element of statistical mechanics or thermodynamics is needed for the development of a biological topic, a review of that element will be provided in lecture and further explained in recitation sections. Each of the topics covered in the course will be provided to students in the form of typewritten text which can be found in the Lecture Notes on the course website.

The topics to be discussed during the term are as follows:

I. Review of Statistical Mechanics and Thermodynamics

Concept of entropy, microcanonical ensemble, fundamental equations of thermodynamics, the chemical potential. The thermodynamic potentials: equations of state, phase equilibria, Clapeyron equation, multicomponent systems, phase equilibria, aqueous solution of biological molecules, osmotic pressure, Poisson Boltzmann equation. Reactions and reaction equilibria, pH and pH control-buffers. Random walk and diffusion. Ligand binding to macromolecules - the binding polynomials. Wyman linkage relations between interacting ligands.

II. Proteins as Stores and Transporters: The Respiratory Proteins

Experimental data on the binding of ligands to hemoglobin. Oxygen dissociation curve, effect of pH, effect of organic phosphates, effect of CO2. Heterotropic and homotropic interaction, cooperativity, allosteric control, linkage between heterotropic ligands. Statistical thermodynamics of binding of ligands to distinct sites on multisubunit proteins: The Pauling, and the Monod-Wyman-Changeaux models of homotropic interactions in hemoglobin. Allosteric model for heterotropic interaction in hemoglobin. Theory of the Bohr effect - pH as a modulator of oxygen binding to hemoglobin.

III. Biological Physics of the Eye and Vision

Basic anatomy, physiology and pathophysiology of the visual system. Cornea, ciliary body, aqueous humour dynamics, iris, ciliary muscles and the lens. History of the development of spectacles. Theory of transparency of the eye: normal and pathological corneas. Scattering of light from the normal and cataractous lens. Discovery of high molecular weight protein aggregates. Observation of Brownian movement of lens proteins. The method of optical mixing spectroscopy. Liquid-liquid and solid-liquid phase transition in concentrated protein solution. Protein condensation diseases. Threshold detection of light at low and high light levels. Light detection as signal to noise discrimination. The molecular basis of phototransduction. The role of rhodopsin, transducin (G protein), phosphodiesterase and cyclic GMP as a cascade for the transduction of light into an electrical response. The theory of the gain and kinetics of the G protein cascade.

IV. Theory of Action Potentials, Simplified Neural Network Models, and Neural Basis of Short Term Memory

V. Random Walks and Diffusion in Biological Systems

VI. Feedback, Control and Homeostasis in Physiological Systems

General role of feedback and control on a molecular level (metabolic pathways) and an organ level (physiological control loops). The human respiratory system and basic model of CO2 control. The system, the controller, the concept of open and closed loop gain. Transient behavior of CO2 proportional control system. Time delays and instability in control. Control during exercise and at high altitudes. Control of blood glucose and the theory of control of enzyme activity at the molecular level.

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