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 |
|
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 |
|
3 |
Multivalent Binding Equilibria
Allostery and Cooperativity
Interaction Free Energy
Avidity and Effective Concentration (Jencks)
Receptor Crosslinking Models |
Homework 1 due |
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) |
Homework 2 due |
6 |
Measurement of Binding Equilibria
SPR
Optical Spectroscopy
Microplate Assays
Cell Surface Titration
Calorimetry, Ultracentrifugation |
|
7 |
Diffusion Limits in Association Kinetics
Shoup/Szabo and Burg/Purcell Surface Diffusion
Local Depletion and Recapture
Smoluchowski Diffusion Limit
Orientation-dependent Interactions |
Homework 3 due |
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 |
Homework 4 due |
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 |
Homework 5 due |
12 |
Complex Reactions and Interactions
Student Presentations on Assigned Papers |
|
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 |
Model implementation 1 due |
14 |
Protein Lifecycles and Localization
Student Presentations on Assigned Papers |
|
15 |
Probability
Poisson Processes
Derivation of Poisson Distribution
Exponential Waiting Times
Example of Leukocyte Rolling
Monte Carlo Simulations
Random Number Generation
Simulations |
Model implementation 2 due |
16 |
Noise in Biology
Student Presentations on Assigned Papers |
|
17 |
Cell Growth Kinetics and Bioreactors
Balanced Growth, Stoichiometry, Monod
Classifications, Segregated and Structured
Chemostat Balance and Washout |
Model implementation 3 due |
18 |
Networks and Systems
Chemotaxis
Basic Control Theory and Robustness |
Homework 6 due |
19 |
Populations
Student Presentations on Assigned Papers |
|
20 |
Fundamentals of Nonlinear Dynamics
Linear Systems of ODEs
Fixed Point Classification
Linearization and Local Stability
Bifurcations |
Model implementation 4 due |
21 |
Gene Expression - Hysteresis and Switches
Student Presentations on Assigned Papers |
|
22 |
Gene Expression: Oscillations
Student Presentations on Assigned Papers |
Model implementation 5 due |
23 |
Spatial heterogeneity: Diffusion and Pharmacokinetics
Student Presentations on Assigned Papers |
Model implementation 6 due |
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 |
|