ICBS: a database of interactions between protein chains mediated by β-sheet formation

Motivation: Interchain β-sheet (ICBS) interactions occur widely in protein quaternary structures, interactions between proteins and protein aggregation. These interactions play a central role in many biological processes and in diseases ranging from AIDS and cancer to anthrax and Alzheimer's. Results: We have created a comprehensive database of ICBS interactions that is updated on a weekly basis and allows entries to be sorted and searched by relevance and other criteria through a simple Web interface. We derive a simple ICBS index to quantify the relative contributions of the β-ladders in the overall interchain interaction and compute first- and second-order statistics regarding amino acid composition and pairing at different relative positions in the β-strands. Analysis of the database reveals a 15.8% prevalence of significant ICBS interactions, the majority of which involve the formation of antiparallel β-sheets and many of which involve the formation of dimers and oligomers. The frequencies of amino acids in ICBS interfaces are similar to those in intrachain β-sheet interfaces. A full range of non-covalent interactions between side chains complement the hydrogen-bonding interactions between the main chains. Polar amino acids pair preferentially with polar amino acids and non-polar amino acids pair preferentially with non-polar amino acids among antiparallel (i, j) pairs. We anticipate that the statistics and insights gained from the database will guide the development of agents that control interchain β-sheet interactions and that the database will help identify new protein interactions and targets for these agents. Availability: The database is available at: http://www.igb.uci.edu/servers/icbs/ Supplementary Information: http://www.igb.uci.edu/servers/icbs/