Bioinformatics Advance Access published online on January 29, 2009
Bioinformatics, doi:10.1093/bioinformatics/btp058
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‘Double water exclusion’: a hypothesis refining the O-ring theory for the hot spots at protein interfaces
Bioinformatics Research Center, & School of Computer Engineering, Nanyang Technological University, Singapore 639798
*To whom correspondence should be addressed. Dr. Jinyan Li, E-mail: JYLi{at}ntu.edu.sg
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Abstract |
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Motivation: The O-ring theory reveals that the binding hot spot at a protein interface is surrounded by a ring of residues that are energetically less important than the residues in the hot spot. As this ring of residues are served to occlude water molecules from the hot spot, the O-ring theory is also called ‘water exclusion’ hypothesis. We propose a ‘double water exclusion’ hypothesis to refine the O-ring theory by assuming the hot spot itself is water-free. To computationally model a water-free hot spot, we use a biclique pattern that is defined as two maximal groups of residues from two chains in a protein complex holding the property that every residue contacts with all residues in the other group.
Methods & Results: Given a chain pair A and B of a protein complex from the Protein Data Bank (PDB), we calculate the interatomic distance of all possible pairs of atoms between A and B. We then represent A and B as a bipartite graph based on these distance information. Maximal biclique subgraphs are subsequently identified from all of the bipartite graphs to locate biclique patterns at the interfaces. We address two properties of biclique patterns: a nonredundant occurrence in PDB, and a correspondence with hot spots when the solvent accessible surface area (SASA) of a biclique pattern in the complex form is small. 1293 biclique patterns are discovered which have a non-redundant occurrence of at least 5, and which each have a minimum 2 and 4 residues at the two sides. Through extensive queries to the HotSprint and ASEdb databases, we verified that biclique patterns are rich of true hot residues. Our algorithm and results provide a new way to identify hot spots by examining proteins' structural data.
Availability: The biclique mining algorithm is available at http://www.ntu.edu.sg/home/jyli/dwe.html.
Contact: J. Li at email address jyli{at}ntu.edu.sg
Associate Editor: Prof. Thomas Lengauer
Received on November 3, 2008; revised on January 2, 2009; accepted on January 23, 2009
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