Notes

Outline

Computer Modeling in Cell Biology Why use computational approaches?

Discussion Overview Computational what? Computational Science, biology and modeling overview What does a computational kinetic/numerical model look like?  Example: Glucose metabolism Computing resources NSF and NIH Get involved National Computational Science Institute (NCSI), Conference sessions.

Computational Biology Computational Biology ¹ Bioinformatics More than sequences, database searches, statistics or image analysis. A part of Computational Science Using mathematical modeling, simulation and visualization Complementing theory and experiment

Models everywhere Theoretical Physical: chemical building blocks… Animal: drosophila, arabidopsis… Data models: graphs, data presentation Mathematical and numerical

Cell Biologist use computational models…

Computation: adding to your method toolkit. Why? To ask questions when experimental cost is prohibitive. To obtain higher degrees of resolution (time steps that may be experimentally intractable). To change variables that can not other wise be manipulated To ask “What if…” questions.

Adding to your method toolkit How: Learn model construction Choose a form of mathematical description Choose an existing computer program OR develop your own for simulation Visualize and analyze your results

Walking through a Computational Model: Glucose Concept Map Factors and relationships between them Describe relationships as set of rules Implement rules in some mathematical form Solve equations: using computer tools View results

Glucose: Concept Map Concept Maps Often drawings, schematics or chemical reactions

Glucose: Factors and Relationships Factors: carbon molecules Relationships: enzyme catalyzed phoshorylation and isomerization

Glucose: Set Rules Rule 1:  Use paper and pen to write your own rule that describes Glucose-6-phosphate in terms of the other factors (variables) in the concept map.

Glucose: My examples of rules

Glucose: Rule for rates of change Refining Rule 1: The rate of change of Glucose-6-phosphate is the rate of Glucose conversion minus the rate of conversion to Fructose-6-phosphate.

The math of rule 1 Substrates Glucose: Glucose- 6-phosphate: Rate constants Enzyme1: Enzyme2:

Some Available Tools General Stella Install Mac or PC Excel Install Mac or PC Customized GEPASI Install Mac or PC Virtual Cell Browser: Java Mac or PC Concept mapping and system dynamics (changes over time). Discrete events, algebraic equations Biochemical kinetics and kinetic analyses. Icon mapping, dynamics and space

Stella

GEPASI

Online Glycolysis models

Results Viewed as graphs File of numbers Virtual Cell (not shown) allows results to be shown in spatial geometries.

Calcium Dynamics

Computation at ASCB Sunday: Minisymposium 8 “Computational Approaches to Cell Biology,” 3:40-5:45 Monday: Education Initiative Forum  “Modeling in undergraduate cell biology and computational science,” 9:15-10am Monday: Poster session “Bioinformatics and Computational Cell Biology,” B745-B761

Presentation Notes Not discussed here: Stochastic models Boolean rule based models Some biological systems are better described by stochastic models Only a sampling of modeling tools are presented.

Resources Computer resources and support: Partnerships for Advanced Computational Infrastructure (PACI) http://alliance.ncsa.uiuc.edu http://www.sdsc.edu http://www/eot.org Pittsburgh Supercomputing Center    http://www.psc.edu/biomed/

Learning Beyond the Conference National Computational Science Institute, http://www.computationalscience.net  undergraduate faculty. Get handout. BioQUEST, http://www.bioquest.org Summer workshop Virtual Cell, http://nrcam.uchc.edu Workshop for users