searching and analysing 3d protein-ligand structures using

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

wwpdb.org

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X-ray EM NMR

Methods of solving the structures

wwpdb.org

10% NMR Spectroscopy

1% Electron microscopy

88% X-ray crystallography

What is PDB?

PDBe tools and services




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Search bar


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Latest PDB statistics

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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

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.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

pdbe.org

Searching PDBe

pdbe.org

Searching PDBe – facets provide more filtering criteria

pdbe.org

Searching PDBe – sorting options

pdbe.org

Entry page

pdbe.org/4plz

pdbe.org/4plz

Entry page

Entry page

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

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



pdbe.org

Validating protein ligand structures

Error in model building

Geometric outliers

Density fit

pdbe.org


Clashes

Badly built residue

pdbe.org

Error in model building

Validating protein ligand structures Geometric outliers

Ramachandra plot

pdbe.org


Fit to density

pdbe.org


How to find and get this information for an entry?

From PDBe web pages

From validation report

By visualizing entry

Programmatically

pdbe.org


From PDBe web pages

pdbe.org


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

https://www.youtube.com/results?search_query=pdbe

PDBe.org proteindatabank

@PDBeurope

[email protected]

Thanks!

searching and analysing 3d protein-ligand structures using

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