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

Li J, Liu Q - Bioinformatics (2009)

Bottom Line: Maximal biclique subgraphs are subsequently identified from all of the bipartite graphs to locate biclique patterns at the interfaces.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.

View Article: PubMed Central - PubMed

Affiliation: Bioinformatics Research Center, School of Computer Engineering, Nanyang Technological University, Singapore 639798. jyli@ntu.edu.sg

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.

Availability: The biclique mining algorithm is available at http://www.ntu.edu.sg/home/jyli/dwe.html.

Supplementary information: Supplementary data are available at Bioinformatics online.

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A biclique pattern identified in the PDB protein complex 1A8G that also occurs in other four PDB complexes. Dotted lines between two residues indicate that their distance in 3D space is not larger than the sum of their corresponding van der Waals radii plus the diameter of a water molecule.
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Figure 1: A biclique pattern identified in the PDB protein complex 1A8G that also occurs in other four PDB complexes. Dotted lines between two residues indicate that their distance in 3D space is not larger than the sum of their corresponding van der Waals radii plus the diameter of a water molecule.

Mentions: We describe in detail an example of biclique pattern using Figure 1. This biclique pattern has a non-reduntant occurrence of four in obligate interactions, and a non-redundant occurrence of one in transient interactions. Specifically, this pattern occurs in the interaction between chain A of PDB 1A8G at Leu5-Pro9-Leu24-Thr26-Leu97, and chain B at Thr26-Leu97. See the left panel of Figure 1, where a dotted line represents that the distance between some two atoms of the two residues is not larger than the sum of their corresponding van der Waals radii plus the diameter of a water molecule; the right panel of this figure shows a virtual graph representation of this biclique pattern used in our computational algorithm. One interesting observation is that the residues can be far away in sequence, but they are close to each other in 3D space, exhibiting a full ‘water exclusion’ adjacency.Fig. 1.


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

Li J, Liu Q - Bioinformatics (2009)

A biclique pattern identified in the PDB protein complex 1A8G that also occurs in other four PDB complexes. Dotted lines between two residues indicate that their distance in 3D space is not larger than the sum of their corresponding van der Waals radii plus the diameter of a water molecule.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2654803&req=5

Figure 1: A biclique pattern identified in the PDB protein complex 1A8G that also occurs in other four PDB complexes. Dotted lines between two residues indicate that their distance in 3D space is not larger than the sum of their corresponding van der Waals radii plus the diameter of a water molecule.
Mentions: We describe in detail an example of biclique pattern using Figure 1. This biclique pattern has a non-reduntant occurrence of four in obligate interactions, and a non-redundant occurrence of one in transient interactions. Specifically, this pattern occurs in the interaction between chain A of PDB 1A8G at Leu5-Pro9-Leu24-Thr26-Leu97, and chain B at Thr26-Leu97. See the left panel of Figure 1, where a dotted line represents that the distance between some two atoms of the two residues is not larger than the sum of their corresponding van der Waals radii plus the diameter of a water molecule; the right panel of this figure shows a virtual graph representation of this biclique pattern used in our computational algorithm. One interesting observation is that the residues can be far away in sequence, but they are close to each other in 3D space, exhibiting a full ‘water exclusion’ adjacency.Fig. 1.

Bottom Line: Maximal biclique subgraphs are subsequently identified from all of the bipartite graphs to locate biclique patterns at the interfaces.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.

View Article: PubMed Central - PubMed

Affiliation: Bioinformatics Research Center, School of Computer Engineering, Nanyang Technological University, Singapore 639798. jyli@ntu.edu.sg

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.

Availability: The biclique mining algorithm is available at http://www.ntu.edu.sg/home/jyli/dwe.html.

Supplementary information: Supplementary data are available at Bioinformatics online.

Show MeSH
Related in: MedlinePlus