A session wise schedule of readings is provided in the table below.


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


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



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


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

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


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

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