BNFO 601 
Integrated Bioinformatics
Scenarios
Fall 2011 
Modeling a metabolic pathway

Scientific story (html)

In brief: Sleeping sickness may be treatable by a drug that targets a glycolytic enzyme... but which one? Your task is to model glycolysis so that the effects of inhibiting each enzyme can be predicted.
Bioinformatic tools
Numerical solution of set of differential equations
     Model reality by differential equations that describe change from current state
Molecular biology concepts: Constructing rate equations from metabolic constants

Perl focus: Functions that use and/or produce arrays

Programs

Argument_test1.pl - Program to aid understanding of @_ and argument lists in Perl (simple case)

Argument_test2.pl - Program to aid understanding of @_ and argument lists in Perl (wrong way to handle list arguments)

Argument_test3.pl - Program to aid understanding of @_ and argument lists in Perl (right way to handle list arguments)

ADP-As.pl - Simple program that models simple zero order reaction

Plot_function.pl - Simple program that calculates y=f(x) [you provide the function] and saves points to file for plotting by Excel

Glycolysis.pl - Model of glycolysis

Integrate.pl - Simple program to illustrate numerical integration

Notes
Introduction to Metabolic Modeling (PDF) (Questionnaire) (Presentation)
Rate equations for enzymatically catalyzed reactions (Presentation)
Tour of Eisenthal & Cornish-Bowdin and the modeling program (PDF) (Questionnaire) (Presentation)
Modeling program (PDF)  (Questionnaire) (Presentation1) (Presentation2)
Compartmentalization and inhibition (PDF)  (Questionnaire)   (Questionnaire after 5th day)
Problem Set: Just one for this scenario (PDF)
For problem 13: data set 1       data set 2

Articles

Voit, Eberhard O (2002). Metabolic modeling: a tool of drug discovery in the post-genomic era. Drug Discovery Today 7:621-628.
Deep background. We won't discuss this article, but it might be of interest regarding the value of metabolic modeling.
Eisenthal, Robert and Cornish-Bowden, Athel (1998). Prospects for Antiparasitic Drugs: The case of Trypanosoma brucei, the causative agend of African sleeping sickness. J Biol Chem 273:5500-5505.
The basis for the model we'll construct in class. Parts of it need to be digested thoroughly. But this is a tough article, and parts of it also can/should be left alone. We'll discuss this article in class, so bring questions.