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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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Related in: MedlinePlus

The biclique pattern in PDB 1A8G with the five hot residues—Leu5-Pro9-Leu24-Thr26-Leu97—in chain A, and two hot residues—Thr26-Leu97—in chain B (best viewed in color). (a) The biclique shaped in 3D space like a groove-anchor, exhibiting an inner ‘water exclusion’. (b) The biclique as a hot spot embedded in the binding interface between chain A and chain B, surrounded by neighbor residues of large SASA.
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Figure 2: The biclique pattern in PDB 1A8G with the five hot residues—Leu5-Pro9-Leu24-Thr26-Leu97—in chain A, and two hot residues—Thr26-Leu97—in chain B (best viewed in color). (a) The biclique shaped in 3D space like a groove-anchor, exhibiting an inner ‘water exclusion’. (b) The biclique as a hot spot embedded in the binding interface between chain A and chain B, surrounded by neighbor residues of large SASA.

Mentions: This nice picture is depicted in Figure 2 which was plotted by the PyMOL software (DeLano, 2002a). A lock-and-key architecture can be clearly observed in the left panel: the five hot residues from chain A form the lock (or groove), while the two hot residues from chain B act as a key. This is in agreement with the mechanism of ‘anchoring residues’ in protein–protein interactions (Rajamani et al., 2004), which explains the kinetically low structural rearrangement of the residues during the formation of complex.Fig. 2.


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

Li J, Liu Q - Bioinformatics (2009)

The biclique pattern in PDB 1A8G with the five hot residues—Leu5-Pro9-Leu24-Thr26-Leu97—in chain A, and two hot residues—Thr26-Leu97—in chain B (best viewed in color). (a) The biclique shaped in 3D space like a groove-anchor, exhibiting an inner ‘water exclusion’. (b) The biclique as a hot spot embedded in the binding interface between chain A and chain B, surrounded by neighbor residues of large SASA.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

Figure 2: The biclique pattern in PDB 1A8G with the five hot residues—Leu5-Pro9-Leu24-Thr26-Leu97—in chain A, and two hot residues—Thr26-Leu97—in chain B (best viewed in color). (a) The biclique shaped in 3D space like a groove-anchor, exhibiting an inner ‘water exclusion’. (b) The biclique as a hot spot embedded in the binding interface between chain A and chain B, surrounded by neighbor residues of large SASA.
Mentions: This nice picture is depicted in Figure 2 which was plotted by the PyMOL software (DeLano, 2002a). A lock-and-key architecture can be clearly observed in the left panel: the five hot residues from chain A form the lock (or groove), while the two hot residues from chain B act as a key. This is in agreement with the mechanism of ‘anchoring residues’ in protein–protein interactions (Rajamani et al., 2004), which explains the kinetically low structural rearrangement of the residues during the formation of complex.Fig. 2.

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