Calendar

LEC # TOPICS KEY DATES
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

 

Course Info

As Taught In
Fall 2004
Level
Learning Resource Types
Problem Sets
Programming Assignments