Presented at University of Southern California, Computational Molecular Biology (3/7/02)

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Table of Contents

Thermodynamics of Living Biochemical Processes

What is the Classic thermodynamics?

The mathematical methods of probability and stochastic processes, and statistical thermodynamics.

Classic biochemistry: understanding biological processes inside living cells and organisms in terms of atoms and molecules.

A non-living system approaches a thermodynamic equilibrium.

A elementary chemical reaction and the law of mass action

Chemical equilibrium

Chemical nonequilibrium steady-state

1st and 2nd Laws of Thermodynamics

Application to motor protein energy transduction

From Muscle to Actin & Myosin

Gliding of actin filaments

Experimental Images

How motor protein generate force?

Stochastic Kinetic Model of a Single Motor Protein

Nonequilibrium Steady-state

Energy Conservation

Efficiency of a motor protein:

Isometric Force and Equilibrium

Protein Structures

Free Energy Landscape of Motor Proteins: the Power Stroke and the Ratchet”

Equation for Motor Protein Movement

Stochastic Macromolecular Mechanics of Single Molecule

The Mathematics of Stochastic Macromolecular Mechanics

Application to GTPase signal transduction and kinetic timing hypothesis

Receptor-mediated GTPase: a timer

Exponential distribution

Kinetic Model for GTPase timer

Model Parameters

Waiting time distributions

Microscopy: wild-type Rab5

Microscopy: Q79L Rab5 mutant

Data: wild-type Rab5

Data: Q79L Rab5

Single Molecule Timer and Kinetic Timing Hypothesis

The Mathematical Basis of Kinetic Timing Hypothesis

Application to analyzing large-scale complex biochemical networks

Major Reactions of Metabolism

Stoichiometric Matrix

Flux Balance Analysis

A Simple Example

E. coli Growth Objective Function

Indentifying an essential gene when the maximal biomass output is sufficiently low

In silico Predictions

Energy Balance Analysis

How EBA work

Energy Balance Equation

How does EBA improve in silico modeling

Biochemical Networki Theory

An Example

Gene regulation and biochemical conductance

Results

What do we learn from EBA?

Conclusions

Acknowledgement

Author: Hong Qian

Email: qian@amath.washington.edu

Home Page: http://www.amath.washington.edu/~qian