p3d @EuroSciPy2010 by C. Fufezan

transcript

High-throughputstructural bioinformatics

using Python & p3d

Dr. C. FufezanInstitute for Biochemistry and Biotechnology of Plants (IBBP)

Overview

Background

p3d overview

example ATP binding site

Fufezan, C. and Specht M. (2009) BMC Bioinformatics 10, 258

http://p3d.fufezan.net

http://github.com/fu/p3d clone us - fork us!

Background

chain(s) of amino acids ...N D R P A I M K

... form proteins

oxygennitrogen

carbon

Background

... form proteins

oxygennitrogen

carbon

Background

... form proteins

and some bind cofactorse.g. ATPAdenosin-tri-phosphate

oxygennitrogen

carbon

Background

knowledge based approaches to elucidate structural factors that are essential for co-factor binding - protein engineering- protein folding- co-factor tuning

proteinsSTRUCTURE O FUNCTION O BIOINFORMATICS

ISSN 0887-3585

A PDB Survey of Heme Ligands in Proteins

Articles published online in Wiley InterScience, 9 May 2008–19 August 2008

V O L U M E 7 3 , N U M B E R 3 , N O V E M B E R 1 5 , 2 0 0 8

Proteins_c1_sp_Ob.qxp 9/11/08 4:14 PM Page 1

Morozov et al. (2004) PNAS, 101, 6946-Huang et al.(2004) PNAS, 101, 5536-Fufezan et al. (2008) Proteins, 73, 690-Negron et al. (2009) Proteins, 74, 400-Fufezan (2010) Proteins, in press

p3d overview

Python module that allows

to access and manipulate protein structure files

rapid development of new screening tools

easily incorporate complex queries

Fufezan, C. and Specht M. (2009) BMC Bioinformatics 10, 258http://p3d.fufezan.net

CG2CG1

x y z idx

atom type

AAchain

residbetaortemperaturefactor

idxatype

aachain

userbeta

protein-object

ATOM Object

idxatype

aachain

userbeta

protein-object

ATOM Object

proteinnot-proteinogenic

chain['A']oxygennitrogen

backboneatype['CA']

Protein Object...

hash...

residues

backbone

oxygen

protein not proteinDr. C. FufezanInstitute for Biochemistry and Biotechnology of Plants (IBBP)

idxatype

aachain

userbeta

protein-object

ATOM Object

backboneatype['CA']

Protein Object...

hash...

residues

backbone

oxygen

idxatype

aachain

userbeta

protein-object

ATOM Object

backboneatype['CA']

Protein Object...

hash...

residues

backbone

oxygen

idxatype

aachain

userbeta

protein-object

ATOM Object

backboneatype['CA']

Protein Object...

hash...

residues

backbone

oxygen

idxatype

aachain

userbeta

protein-object

ATOM Object

backboneatype['CA']

Protein Object...

hash...

residues

backbone

oxygen

idxatype

aachain

userbeta

protein-object

ATOM Object

Tree Object

idxatype

aachain

userbeta

protein-object

ATOM Object

Tree Object

idxatype

aachain

userbeta

protein-object

ATOM Object

Tree Objectquery( Vector1, radius )

idxatype

aachain

userbeta

protein-object

ATOM Object

Tree Objectquery( Vector1, radius )

Vectorsdo not have to

be atoms!!

Protein class

O1 FME A 1

CA PHE A 2

List of atom objects (vectors)

BSP Tree

residues

backbone

oxygen

protein not protein

sets (hashes)

Protein class

O1 FME A 1

CA PHE A 2

BSP Tree

residues

backbone

oxygen

protein not protein

sets (hashes)

Query function using human readable syntaxe.g.: pdb.query(‘backbone and resid 5..12 and within 5 of resname FME’)

Protein class

O1 FME A 1

CA PHE A 2

BSP Tree

residues

backbone

oxygen

protein not protein

sets (hashes)

Protein class

O1 FME A 1

CA PHE A 2

BSP Tree

residues

backbone

oxygen

protein not protein

sets (hashes)

pdb.query(‘resname HOH and within 4 of resname ASP’)

Protein class

O1 FME A 1

CA PHE A 2

BSP Tree

residues

backbone

oxygen

protein not protein

sets (hashes)

pdb.query(‘resname HOH and within 4 of resname ASP’)pdb.query(‘oxygen and not protein’)

Protein class

O1 FME A 1

CA PHE A 2

BSP Tree

residues

backbone

oxygen

protein not protein

sets (hashes)

pdb.query(‘ protein and within 4 of ’, p3d.vector.Vector(x,y,z) )

Protein class

O1 FME A 1

CA PHE A 2

BSP Tree

residues

backbone

oxygen

protein not protein

sets (hashes)

for residueName in pdb.hash[non-aa-resname]:

Protein class

O1 FME A 1

CA PHE A 2

BSP Tree

residues

backbone

oxygen

protein not protein

sets (hashes)

for residueName in pdb.hash[non-aa-resname]: targets = pdb.query(' protein and within 4 of \

Protein class

O1 FME A 1

CA PHE A 2

BSP Tree

residues

backbone

oxygen

protein not protein

sets (hashes)

for residueName in pdb.hash[non-aa-resname]: targets = pdb.query(' protein and within 4 of \ ( resname 'residueName' and oxygen )' )

Example ATP binding

The ATP binding sites

Adenosine-tri-phosphate

ΔG˚' = -30 kJ mol-1

40 kg / day

non. redundant set of proteins24 binding sites

The ATP binding site

hydropathy index

Observations

Summary

p3d allows to develop quickly Python scripts to screen Protein structures

combines Vectors, sets and BSPTree

p3d allows flexible and complex queriesusing human readable language

Acknowledgements

M. SpechtProf. Dr. M. Hippler

founding by the DFG and Alexander von Humboldt Stiftung

p3d @EuroSciPy2010 by C. Fufezan

Education