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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
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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
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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
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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
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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
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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
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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. |
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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. |
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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. |
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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. |
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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. |
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Pharmacokinetics Plasma Clearance Kinetics and Mechanisms One and Two Compartment Models Physiological Models Formulation and Bioavailability |
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25 |
Transport Effects on Biomolecular Interactions Weisz Analysis, Thiele Modulus, Damkohler # Shrinking Core Model and Tumor Penetration | |