'Double water exclusion': A hypothesis refining the O-ring theory for the hot spots at protein interfaces

Li, J; Liu, Q

'Double water exclusion': A hypothesis refining the O-ring theory for the hot spots at protein interfaces

Li, J

Liu, Q

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Publication Type:: Journal Article
Citation:: Bioinformatics, 2009, 25 (6), pp. 743 - 750
Issue Date:: 2009-03-01

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Field	Value	Language
dc.contributor.author	Li, J https://orcid.org/0000-0003-1833-7413	en_US
dc.contributor.author	Liu, Q	en_US
dc.date.issued	2009-03-01	en_US
dc.identifier.citation	Bioinformatics, 2009, 25 (6), pp. 743 - 750	en_US
dc.identifier.issn	1367-4803	en_US
dc.identifier.uri	http://hdl.handle.net/10453/14874
dc.description.abstract	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 is 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 and 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 non-redundant 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. A total of 1293 biclique patterns are discovered which have a non-redundant occurrence of at least five, and which each have a minimum two and four 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. © 2009 The Author(s).	en_US
dc.relation.ispartof	Bioinformatics	en_US
dc.relation.isbasedon	10.1093/bioinformatics/btp058	en_US
dc.subject.classification	Bioinformatics	en_US
dc.subject.mesh	Water	en_US
dc.subject.mesh	Proteins	en_US
dc.subject.mesh	Computational Biology	en_US
dc.subject.mesh	Protein Conformation	en_US
dc.subject.mesh	Algorithms	en_US
dc.subject.mesh	Thermodynamics	en_US
dc.subject.mesh	Models, Molecular	en_US
dc.subject.mesh	Databases, Protein	en_US
dc.title	'Double water exclusion': A hypothesis refining the O-ring theory for the hot spots at protein interfaces	en_US
dc.type	Journal Article
utslib.citation.volume	6	en_US
utslib.citation.volume	25	en_US
utslib.for	080110 Simulation and Modelling	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	01 Mathematical Sciences	en_US
utslib.for	06 Biological Sciences	en_US
utslib.for	08 Information and Computing Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Strength - AAI - Advanced Analytics Institute Research Centre
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	closed_access
pubs.issue	6	en_US
pubs.publication-status	Published	en_US
pubs.volume	25	en_US

Abstract:

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 is 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 and 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 non-redundant 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. A total of 1293 biclique patterns are discovered which have a non-redundant occurrence of at least five, and which each have a minimum two and four 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. © 2009 The Author(s).

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http://hdl.handle.net/10453/14874