Searching and Analysing 3D Protein-ligand Structures using PDBe web services Abhik Mukhopadhyay www.pdbe.org
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Searching and Analysing 3D Protein-ligand Structures using PDBe web services
Abhik Mukhopadhyay
www.pdbe.org
About wwPDB and PDBe
PDBe web services
Searching PDBe – A case study
Validation of Protein ligand structures
pdbe.org
What is the Protein Data Bank (PDB)?
pdbe.org
An archive of experimentally determined 3-dimensional structures of biological macromolecules Protein, nucleic acids, small molecules
Available to anyone for free
wwpdb.org
‘The PDB’ FTP Archive
wwPDB.org
‘The PDB’ FTP Archive
Value added data
Value added data
Value added data
Value added data
PDB growth over time
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X-ray EM NMR
Methods of solving the structures
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10% NMR Spectroscopy
1% Electron microscopy
88% X-ray crystallography
What is PDB?
PDBe tools and services
Searching PDBe – A case study
Validation of Protein ligand structures
PDBe tools and services
pdbe.org
PDBe tools and services
pdbe.org
Search bar
PDBe tools and services
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Latest PDB statistics
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Latest PDB statistics
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PDBe tools and services
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PDBe tools and services
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PDBe tools and services - PDBeChem
pdbe.org/chem
Chemical component dictionary
pdbe.org/chem
• Contains over 26,329 unique chemical components (amino acids/nucleotides, small molecule ligands, solvents..)
• For each unique chemical component:
• Unique 3 letter code
• Name, systematic & synonym
• Chemical formula
• SMILES, InChI…
• Stereo configuration of atoms and bonds in cases of stereo-isomers (R/S – E/Z)
• Ideal and representative 3D coordinates
AMODIAQUINE
CQA
PDBe tools and services - PDBeChem
pdbe.org/chem
PDBe tools and services - PDBeChem
pdbe.org/chem
PDBe tools and services - PDBeChem
pdbe.org/chem
PDBe tools and services - PDBeChem
pdbe.org/chem
PDBe tools and services - PDBeChem
pdbe.org/chem
PDBe tools and services - PDBeChem
pdbe.org/chem
PDBe tools and services - PDBeChem
pdbe.org/chem
PDBe tools and services - PDBeChem
pdbe.org/chem
Accessing chemistry related information using REST-API
What hetcode present in entry
Information about hetcode
Functional annotation, and
mapping
pdbe.org
PDBe REST-API
https://www.youtube.com/AUcTgIBdGj8
API also makes it possible to access structure-related information in
manageable data blocks
Designed to provide programmatic access to all information in the PDBe
database
For easy access, the API contains separate modules
pdbe.org/api
PDBe REST-API
https://www.youtube.com/AUcTgIBdGj8
Other popular PDBe services
• PDBeFold
comparison and 3D alignment of protein structures
examination of a protein structure for structure based similarity with the
whole PDB
pdbe.org/fold
Other popular PDBe services
• PDBePISA
Tool to investigate formation of macromolecular interfaces and stability
Retrieve pre-calculated results for the whole PDB archive.
pdbe.org/pisa
SIFTS
pdbe.org/sifts
What is PDB?
PDBe tools and services
Searching PDBe – A case study
Validation of Protein ligand structures
pdbe.org
Searching the PDB made simple
At PDBe we’ve implemented:
• Auto-complete suggestions
• Facets to narrow down search results
• Quality presented on search results
• Four views of results
• Moving away from entry-centricity
pdbe.org
Searching PDBe
pdbe.org
PDBe search bar
https://www.youtube.com/watch?v=V4bxxbqcaLU
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Searching PDBe
pdbe.org
Searching PDBe – facets provide more filtering criteria
pdbe.org
Searching PDBe – facets provide more filtering criteria
pdbe.org
Searching PDBe – sorting options
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Entry page
pdbe.org/4plz
Entry page
pdbe.org/4plz
pdbe.org/4plz
Entry page
pdbe.org/4plz
Entry page
Entry page
pdbe.org/4plz
Entry page
pdbe.org/4plz
Entry page – Different download options
pdbe.org/4plz
Entry page – Different download options
pdbe.org/4plz
Entry page – Visualization option
pdbe.org/4plz
3D visualization – Litemol viewer, interactive web-based visualization
https://www.youtube.com/watch?v=JMeXDIbssdQ
pdbe.org/4plz
3D visualization – Litemol viewer, interactive web-based visualization
pdbe.org/4plz
Features in Litemol
Green and red map shows extra or missing atoms
Shows 3D-SNFG representation of sugars
Options to show domain annotation pfam Interpro Cath
Entry images – Unique molecule, By annotation, By domain
pdbe.org/4plz
Ligand and environment
Litemol viewer – shows ligand with density Ligplot – shows environment
pdbe.org
Ligand and environment
pdbe.org
Ligand and environment
pdbe.org
Ligand and environment
pdbe.org
Functional annotation of ligand – Cofactor
Not an inherent property of ligand
Entry specific
Other biological information defines
function
pdbe.org
Searching PDB programmatically
Resolution distribution
R-Free distribution
pdbe.org
https://github.com/PDBeurope/pdbe-api-training
Searching PDB programmatically
Mol wt distribution of all hetcodes
Mol wt distribution of hetcodes between mol. Wt. 100-500
pdbe.org
https://github.com/PDBeurope/pdbe-api-training
About WWPDB and PDBe
PDBe web services
Searching PDBe – A case study
Validation of Protein ligand structures
pdbe.org
Validating protein ligand structures
Error in model building
Geometric outliers
Density fit
pdbe.org
Validating protein ligand structures
Clashes
Badly built residue
pdbe.org
Error in model building
Validating protein ligand structures Geometric outliers
Ramachandra plot
pdbe.org
Validating protein ligand structures
Fit to density
pdbe.org
Validating protein ligand structures
Fit to density
pdbe.org
Validating protein ligand structures
How to find and get this information for an entry?
From PDBe web pages
From validation report
By visualizing entry
Programmatically
pdbe.org
Validating protein ligand structures
From PDBe web pages
pdbe.org
Validating protein ligand structures
pdbe.org
How well does the model back-predict the data?
Atoms bumping into each other
Surprising bond angles
Atoms not in electron density
Validating protein ligand structures From validation report
Overall quality at a glance
Red bar on top shows residue with poor fit to density
pdbe.org
Validating protein ligand structures From validation report
Ligand information in overall quality at a glance section
Ligand with chirality error
pdbe.org
Validating protein ligand structures By visualizing entry
Viewing in litemol
pdbe.org
Validating protein ligand structures By visualizing entry
Viewing ligand in ligand and environment page
It is possible to access this data also programmatically, by using PDBe aPI,
pdbe.org
PDBe resources
Tutorials and documentations in PDBe training page
pdbe.org/training
PDBe you tube channel –
https://www.youtube.com/results?search_query=pdbe
More PDBe tutorials at EMBL-EBI train online
pdbe.org
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