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PREDICTION OF PROTEIN-PROTEIN INTERACTIONS FROM EVOLUTIONARY INFORMATION
INTRODUCTION
The more we know about the molecular biology of the cell, the more we see genes and proteins as part of networks or pathways instead of as isolated entities and understand their function as a variable of the cellular context. To fulfill this new paradigm, genomic sequences offer a catalog of building blocks, and protein interactions provide the first information for the challenging task of understanding the functions of these genes and proteins within their situation in networks and pathways. To further refine the information on the context and timing in which these observed biological functions take place, additional insight from genetic regulatory mechanisms and genetic specificity (cell-type specificity, individual differences, etc.) will become increasingly important.
The study of protein interactions can be divided into two complementary aspects, the determination of the residues or regions implicated in the interactions and the deciphering of the identity of the interaction partners (which proteins interact with which ones). These two problems have been typically addressed by biophysical and biochemical techniques, such as binding studies (chromatographic isolation of complexes, coimmunoprecipitation, protection, cross-linking studies, etc.) and indirect genetic methods (gene suppression studies, systematic mutagenesis, and interspecies exchanges). ...
