Biomacromolecular structure analysis
- detection of patterns
Radka Svobodová
CEITEC, Masaryk University
PatternQuery: Description and detection of
fragments
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▪ Describes a fragment based on its topology and geometry
▪ Extracts the fragment from all structures in Protein Data
Bank
Sehnal D., Pravda L., Svobodová R., Ionescu C.-M., Koča J. (2015) PatternQuery: web application for fast detection of
biomacromolecular structural patterns in the entire Protein Data Bank. Nucleic Acids Res., 43, W383–W388.
http://ncbr.muni.cz/PatternQuery
Detection: Why to detect biomacromolecular parts?
Fragments:
• Patterns for drug design
• Comparison of biomacromolecules
• Understanding / discovery of biomaromolecule function
Channels:
• Key objects for biomacromolecule function
• Influence the binding site selectivity (only some substrate can path through)
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Detection: How to detect biomacromolecular fragments?
• Methodology:
• Describe a fragment via a defined expression (query)
• Find all suitable fragments
• Tools: PatternQuery, RASMOT-3D PRO, Promotif, Prosite, IMAAAGine,
PDBeMotif, SPRITE& ASSAM, 3Dfit, SPASM, Protein segment finder
Figure: Detection of testosterone (TES) and its 4 Å large surrounding
via PatternQuery: A query and a picture of the detected fragment.
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Detection: Example – binding pocket detection
Detection of fragments within 3U7Y
• Glycoprotein gp160 from Human immunodeficiency virus 1 in
complex with Homo sapiens immunoglobulins (PDB ID 3u7y).
• Goal: Detect a binding pocket of any residue containing a pyranose
• Results - via PatternQuery (http://ncbr.muni.cz/PatternQuery):
A) First, the query identifies a pyranose moiety (a ring composed of 5 carbons and
an oxygen atom). B) Then, all residues which include this pattern in their structure
are identified. C) Finally, all the residues that are at most 4Å from any of the
pyranose containing residues are detected as well.
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PatternQuery - Detecion of key parts
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Near(4,
Rings(5 * ["C"] + ["O"]),
Near(4, Atoms("Ca"), Atoms("Ca"))
)
.AmbientResidues(4)
Sugar binding site from Pseudomonas aeruginosa lectin
Results (38 entries from PDB):
• Pseudomonas aeruginosa (27 entries) or its synthetic construct (2 entries)
• Burkholderia cenocepacia (4 entries)
• Ralstonia solanacearum (2 entries)
• Chromobacterium violaceum (2 entries)
• Bacillus subtilis (1 entry)
Software PatternQuery:
Sehnal, Pravda, Svobodová, …, Koča, Nucl.
Acids Res. (2015)
Comparison
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Superimposition of sugar binding sites
from Pseudomonas aeruginosa lectin:
Results:
Two main types of binding sites:
• Pseudomonas aeruginosa: 2 SER
• Burkholderia cenocepacia and Ralstonia solanacearum: 2 ALA + HIS
Plus their combination:
• Chromobacterium violaceum, Pseudomonas aeruginosa mutants: 1 ALA, 1 SER
~
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Software SiteBinder: Sehnal, Svobodová, ..., Koča, J. Chem. Inf. Model. (2012)
Detection: Example – sugar-binding site detection
Detection of Pseudomonas aeruginosa Lec-B sugar binding site
Pattern: Near(4,
Rings(5 * ["C"] + ["O"]),
Near(4, Atoms("Ca"), Atoms("Ca"))
)
.AmbientResidues(4)
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Results:
The binding site is contained in 40 PDB entries from 4 organisms (bacteria):
• Pseudomonas aeruginosa
• Burkholderia cenocepacia
• Ralstonia solanacearum
• Chromobacterium violaceum