p3d @EuroSciPy2010 by C. Fufezan

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!



http://github.com/fu/p3d

http://github.com/fu/p3d

Background



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

... form proteins

oxygennitrogen

carbon

Background

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

... form proteins

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

oxygennitrogen

carbon

Background


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

prote

ins

VO

LU

ME

7

3,

N

UM

BE

R

3,

N

OV

EM

BE

R

15

,

20

08

PA

GE

S

52

7–

79

4

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


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


N

CA

CB

CG2CG1

CO

x y z idx

atom type

AAchain

residbetaortemperaturefactor

user


idxatype

aachain

xyz

userbeta

protein-object

ATOM Object

idxatype

aachain

xyz

userbeta

protein-object

ATOM Object

proteinnot-proteinogenic

chain['A']oxygennitrogen

backboneatype['CA']

...

Protein Object...

hash...

residues

backbone

alpha

oxygen

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

idxatype

aachain

xyz

userbeta

protein-object

ATOM Object

Tree Object


idxatype

aachain

xyz

userbeta

protein-object

ATOM Object

Tree Objectquery( Vector1, radius )


idxatype

aachain

xyz

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

alpha

oxygen

protein not protein

sets (hashes)

Protein class

O1 FME A 1

CA PHE A 2


BSP Tree

residues

backbone

alpha

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

alpha

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

alpha

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

alpha

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

alpha

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

alpha

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

alpha

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

The ATP binding sites

non. redundant set of proteins24 binding sites


The ATP binding site


The ATP binding site

+4.5

-4.5

hydropathy index

0

1

10

Observations

non. redundant set of proteins24 binding sites


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

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