Structural systems biology: modelling protein interactions

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Abstract
Much of systems biology aims to predict the behaviour of biological systems on the basis of the set of molecules involved. Understanding the interactions between these molecules is therefore crucial to such efforts. A full understanding of how molecules interact comes only from three-dimensional structures, but structural biology is still difficult for complexes of two or more macromolecules. This makes the methods that are used to predict structural details for interactions of crucial importance. The interactomes for Saccharomyces cerevisiae, Drosophila melanogaster, Caenorhabditis elegans, Helicobacter pylori, Escherichia coli and Homo sapiens that are available at present can be readily complemented by methods that predict interactions on the basis of genome context, expression patterns and using other data sources. The molecular details of interactions can be predicted by protein docking, homology modelling, or identifying recurring interaction-sequence signatures, either a pair of domains or a domain and a short linear peptide. Using these tools, it is possible to predict the structures of large molecular assemblies or the details of how cellular pathways operate. Complementing the interactome with structural information will ultimately produce a more complete whole-cell framework at atomic-level detail, which will have a large impact on the study of biological systems.