Molecular Interactions - Structure and Pathways

Biomath 2006, IMPA - Rio de Janiero, Brazil

Julie C. Mitchell
Mathematics and Biochemistry
University of Wisconsin - Madison

Short Course Abstract

Protein interactions are at the heart of most biological processes. Interactions can be studied at many levels, from the molecular to cellular level and beyond.  The short course will address two important aspects of modeling protein interactions: protein docking and biological pathways.

At the molecular level, proteins bind to other proteins based on biophysical properties.  The characteristics that allow two proteins to bind include surface geometry and charge distribution.  Techniques for understanding protein biophysics are most accurate at the particle level (quantum mechanics), but various approximations can make calculations more tractable.  Through the use of partial differential equations, optimization and Fourier analysis, the approximate protein binding geometry between two proteins can be predicted.

At the systems level, networks of proteins interact within biological pathways.  Most important physiological processes are controlled not by a single interaction between molecules, but rather by a cascade of interactions.  At the structural level, one is concerned with the binding geometry between a pair of molecules.  At the systems level, the frequency of such events is of primary interest.  Each class of molecule becomes a variable in a system of coupled nonlinear differential equations.  Understanding the behavior of these dynamical systems has a multitude of uses within medical science.

Reading Materials

Protein Folding and Docking

Leach, A. R. "Principles of Molecular Modelling"  Cambridge University Press.

Mitchell, J. C. "Protein-protein Interactions: Prediction" (2005) Nature ELS.

Halperin, I., Ma B., Wolfson H. and Nussinov N. (2002) "Principles of docking: An overview of search algorithms and a guide to scoring functions."  Proteins 47(4): 409-43.

Biological Pathways

Voit, E. O. "Computational Analysis of Biochemical Pathways."  Cambridge University Press.

De Jong, H. (2002) "Modeling and Simulation of Genetic Regulatory Systems: A Literature Review."  J. Comp. Biol. 9(1): 67-103.

Tyson, J. J, Chen, K. C., and Novak B. (2003) "Sniffers, buzzers, toggles and blinkers: dynamics of regulatory and signaling pathways in the cell." Curr.  Op. Cell. Biol. 15: 221–231.

Course Materials

Protein Folding and Docking

The first set of lecture notes and the first computer lab. To do the computer lab, you should download the complete set of lab files.

Biological Pathways

The second set of lecture notes and the first computer lab. To do the computer lab, you should download the complete set of lab files.