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


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



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


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

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


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

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