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A session wise schedule of readings is provided in the table below.
Textbook
Lauffenburger, Douglas A., and J. Jennifer Linderman. Receptors: Models for Binding, Trafficking, and Signaling. New York: Oxford University Press, 1995. ISBN: 9780195106633.
Supplemental Texts
Hammes, Gordon G. Thermodynamics and Kinetics for the Biological Sciences. Hoboken, NJ: John Wiley and Sons, 2000. ISBN: 9780471374916.
Creighton, Thomas E. Proteins: Structures and Molecular Properties. 2nd ed. New York, NY: W. H. Freeman and Company, 1993. ISBN: 9780716723172.
Bailey, James, and David F. Ollis. Biochemical Engineering Fundamentals. 2nd ed. Burr Ridge, IL: McGraw Hill Higher Education, 1986. ISBN: 9780070032125.
Steinfeld, Jeffrey I., J. S. Francisco, and W. L. Hase. Chemical Kinetics and Dynamics. 2nd ed. E. Rutherford, NJ: Prentice Hall PTR, 1998. ISBN: 9780137371235.
Cantor, Charles R., and Paul R. Schimmel. Biophysical Chemistry. New York, NY: Worth Publishers, 1980. ISBN: 9780716711889, ISBN: 9780716711902, and ISBN: 9780716711926.
Blanch, Harvey W., and D. S. Clark, eds. Biochemical Engineering. New York, NY: Marcel Dekker, 1997. ISBN: 9780824700997.
Shargel, Leon, et al. Applied Biopharmaceutics and Pharmacokinetics. New York, NY: McGraw-Hill Professional Publishing, 2004. ISBN: 9780071375504.
Carberry, James J. Chemical and Catalytic Reaction Engineering. New York, NY: McGraw-Hill, 1976. ISBN: 9780070097902.
Strogatz, Steven H. Nonlinear Dynamics and Chaos: With Applications to Physics, Biology, Chemistry, and Engineering. Cambridge, MA: Perseus Publishing, 2000. ISBN: 9780738204536.
Readings Text Legend
B&C = Blanch and Clark
B&O = Bailey and Ollis
Cr = Creighton
C&S = Cantor and Schimmel
H = Hammes
L&L = Lauffenburger and Linderman
SFH = Steinfeld, Francisco and Hase
* = These papers are used for Model Implementation Assignments.
| 1 | Noncovalent Biomolecular Interactions
Significance in Cell Function
Measure, Model, Manipulate at Molecular Level
Bonding Forces (HB, VdW, Elec, HE)
Solvation and the Role of Water
Standard States, Free Energy, Kd
Typical Ranges of Affinity, On and Off Rates
Free Energy, Enthalpy, and Entropy
Characteristics of Interfaces
Ala Scan and Double Mutant Cycles | L&L 2.1.2 Cr 4.1-3 H 1.9, 2.7, 3.5-6 |
| 2 | Protein-Ligand Binding Equilibria
Monovalent Reversible Equilibria
Analytic and Pseudo - 1st Order Approx Isotherms
Immobilized Protein/Ligand Interactions
Graphical Representations of Binding Equilibria
Immobilized Protein Binding
Data Plotting and Analysis
Statistics of Multiple Identical Sites | L&L 2.2.1, 2.2.3 Cr 8.2.1 H 6.1-2 |
| 3 | Multivalent Binding Equilibria
Allostery and Cooperativity
Interaction Free Energy
Avidity and Effective Concentration (Jencks)
Receptor Crosslinking Models | L&L 2.2.2, 4.3, 2.2.4 Cr 4.4 H 6.3-4, 6.7-8 |
| 4 | Multivalent Binding Equilibria (cont.)
Immobilized Multivalency (Pluckthun)
Soluble Multivalency and Linker Length (Zhou) | |
| 5 | Spectroscopy and Fluorescence
Interactions of Light w/Matter, Scatter and Absorb
Beer's Law
Fluorescence Theory (Stokes Shift, FRET)
Fluorescence Applications (GFP, FRET, Flow Cytometry, Confocal and 2 Photon Microscopy) | |
| 6 | Measurement of Binding Equilibria
SPR
Optical Spectroscopy
Microplate Assays
Cell Surface Titration
Calorimetry, Ultracentrifugation | H 6.5 |
| 7 | Diffusion Limits in Association Kinetics
Shoup/Szabo and Burg/Purcell Surface Diffusion
Local Depletion and Recapture
Smoluchowski Diffusion Limit
Orientation-dependent Interactions | L&L 4.1-2 C&S 1214 SFH 4.1-5 H 4.6, 5.6 |
| 8 | Temperature and Salt Dependence of Association Kinetics
Arrhenius Dependence and Transition State Theory
Debye-Hückel
Statistics
Global Nonlinear Least Squares
Confidence Intervals on Fit Parameters | |
| 9 | Biomolecular Interaction Kinetics
Analytical and Pseudo 1st - Order Solutions
Relaxation (Perturbation, Temperature Jump)
Double Jump Approach for Hidden Kinetics | L&L 2.2.1.d H 4.8 |
| 10 | Biosensor Data Analysis
Experimental Method and Design
Consistency Checks and Artifacts
Mass Transport Effects and Modeling | |
| 11 | Enzyme Kinetics
Michaelis-Menten Derivation
Reversible Inhibition
Receptor Signaling and Kinases | L&L 5.1.4, 5.2.2, 5.3 H 5.1-5 B&O 3.2-5 B&C 1 |
| 12 | Complex Reactions and Interactions
Student Presentations on Assigned Papers | * Huang, C. F., and J. E. Ferrell. "Ultrasensitivity in the Mitogen-activated Protein Kinase Cascade." PNAS 93 (1996): 10078-83.
Lipschultz, C. A., A. Yee, S. Mohan, Y. Li, and S. J. Smith-Gill. "Temperature Differentially Affects Encounter and Docking Thermodynamics of Antibody-Antigen Association." J Mol Recognit. 15, no. 1 (January, February 2002): 44-52. |
| 13 | Kinetics of Protein Synthesis, Turnover, and Localization
General Material Balance and Growth Dilution
Steady-state and Kinetics of Intracellular Proteins
Receptor Endocytosis and Downregulation
Pulse/Chase
Internalization and Secretion Rates | L&L 3 |
| 14 | Protein Lifecycles and Localization
Student Presentations on Assigned Papers | Haugh, J. M. "Mathematical Model of Human Growth Hormone (hGH)-Stimulated Cell Proliferation Explains the Efficacy of hGH Variants as Receptor Agonists or Antagonists." Biotechnology Progress, in Press 2004.
* Fallon, E. M., and D. A. Lauffenburger. "Computational Model for Effects of Ligand/Receptor Binding Properties on Interleukin-2 Trafficking Dynamics and T Cell Proliferation Response." Biotechnology Progress 16 (2000): 905-16. |
| 15 | Probability
Poisson Processes
Derivation of Poisson Distribution
Exponential Waiting Times
Example of Leukocyte Rolling
Monte Carlo Simulations
Random Number Generation
Simulations | |
| 16 | Noise in Biology
Student Presentations on Assigned Papers | * Rao, C. V., and A. P. Arkin. "Stochastic Chemical Kinetics and the Quasi-Steady-State Assumption: Application to the Gillespie Algorithm." J. Chem Phys 118 (2003): 4999.
Raser, J. M., and E. K. O'Shea. "Control of Stochasticity in Eukaryotic Gene Expression." Science 304, no. 5678 (Jun 18, 2004): 1811-14. |
| 17 | Cell Growth Kinetics and Bioreactors
Balanced Growth, Stoichiometry, Monod
Classifications, Segregated and Structured
Chemostat Balance and Washout | B&O 7, 7.1-2 |
| 18 | Networks and Systems
Chemotaxis
Basic Control Theory and Robustness | L&L 3 |
| 19 | Populations
Student Presentations on Assigned Papers | Perelson, A. S., A. U. Neumann, M. Markowitz, J. M. Leonard, and D. D. Ho. "HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time." Science 271 (1996): 1582-86.
* Kaplan, E. H., D. L. Craft, and L. M. Wein. "Emergency Response to a Smallpox Attack: The Case for Mass Vaccination." PNAS 99 (2002): 10935. |
| 20 | Fundamentals of Nonlinear Dynamics
Linear Systems of ODEs
Fixed Point Classification
Linearization and Local Stability
Bifurcations | |
| 21 | Gene Expression - Hysteresis and Switches
Student Presentations on Assigned Papers | * Gardner, T. S., C. R. Cantor, and J. J. Collins. "Construction of a Genetic Toggle Switch in Escherichia Coli." Nature 403, no. 339 (2000).
Xiong, W., and J. E. Ferrell Jr. "A Positive-Feedback-Based Bistable 'Memory Module' that governs a Cell Fate Decision." Nature 426, no. 6965 (November 27, 2003): 460-65. |
| 22 | Gene Expression: Oscillations
Student Presentations on Assigned Papers | * Tyson, J. J., C. I. Hong, C. D. Thron, and B. Novak. "A Simple Model of Circadian Rhythms Based on Dimerization and Proteolysis of PER and TIM." Biophys J. 77, no. 5 (November 1999): 2411-7.
Gilg, Olivier, Ilkka Hanski, and Benoît Sittler. "Cyclic Dynamics in a Simple Vertebrate Predator-Prey Community." Science 302 (October 31, 2003): 866-68. |
| 23 | Spatial heterogeneity: Diffusion and Pharmacokinetics
Student Presentations on Assigned Papers | Hicks, K. O., F. B. Pruijn, J. R. Sturman, W. A. Denny, and W. R. Wilson. "Multicellular Resistance to Tirapazamine is due to Restricted Extravascular Transport: a Pharmacokinetic/Pharmacodynamic Study in HT29 Multicellular Layer Cultures." Cancer Res. 63, no. 18 (September 15, 2003): 5970-7.
Zhu, H., R. K. Jain, and L. T. Baxter. "Tumor Pretargeting for Radioimmunodetection and Radioimmunotherapy." J Nucl Med. 39, no. 1 (1998): 65-76. |
| 24 | Pharmacokinetics
Plasma Clearance Kinetics and Mechanisms
One and Two Compartment Models
Physiological Models
Formulation and Bioavailability |
|
| 25 | Transport Effects on Biomolecular Interactions
Weisz Analysis, Thiele Modulus, Damkohler #
Shrinking Core Model and Tumor Penetration | |