p3d @euroscipy2010 by c. fufezan
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High-throughputstructural bioinformatics
using Python & p3d
Dr. C. FufezanInstitute for Biochemistry and Biotechnology of Plants (IBBP)
Overview
Background
p3d overview
example ATP binding site
Dr. C. FufezanInstitute for Biochemistry and Biotechnology of Plants (IBBP)
Fufezan, C. and Specht M. (2009) BMC Bioinformatics 10, 258
http://p3d.fufezan.net
http://github.com/fu/p3d clone us - fork us!
Background
Dr. C. FufezanInstitute for Biochemistry and Biotechnology of Plants (IBBP)
Dr. C. FufezanInstitute for Biochemistry and Biotechnology of Plants (IBBP)
chain(s) of amino acids ...N D R P A I M K
... form proteins
oxygennitrogen
carbon
Background
Dr. C. FufezanInstitute for Biochemistry and Biotechnology of Plants (IBBP)
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
Dr. C. FufezanInstitute for Biochemistry and Biotechnology of Plants (IBBP)
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
Dr. C. FufezanInstitute for Biochemistry and Biotechnology of Plants (IBBP)
p3d
Dr. C. FufezanInstitute for Biochemistry and Biotechnology of Plants (IBBP)
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
Dr. C. FufezanInstitute for Biochemistry and Biotechnology of Plants (IBBP)
N
CA
CB
CG2CG1
CO
x y z idx
atom type
AAchain
residbetaortemperaturefactor
user
Dr. C. FufezanInstitute for Biochemistry and Biotechnology of Plants (IBBP)
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
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
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
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
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
Dr. C. FufezanInstitute for Biochemistry and Biotechnology of Plants (IBBP)
idxatype
aachain
xyz
userbeta
protein-object
ATOM Object
Tree Object
Dr. C. FufezanInstitute for Biochemistry and Biotechnology of Plants (IBBP)
idxatype
aachain
xyz
userbeta
protein-object
ATOM Object
Tree Objectquery( Vector1, radius )
Dr. C. FufezanInstitute for Biochemistry and Biotechnology of Plants (IBBP)
idxatype
aachain
xyz
userbeta
protein-object
ATOM Object
Tree Objectquery( Vector1, radius )
Vectorsdo not have to
be atoms!!
Dr. C. FufezanInstitute for Biochemistry and Biotechnology of Plants (IBBP)
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
List of atom objects (vectors)
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
List of atom objects (vectors)
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
List of atom objects (vectors)
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’)
pdb.query(‘resname HOH and within 4 of resname ASP’)
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)
Query function using human readable syntaxe.g.: pdb.query(‘backbone and resid 5..12 and within 5 of resname FME’)
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
List of atom objects (vectors)
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’)
pdb.query(‘resname HOH and within 4 of resname ASP’)pdb.query(‘oxygen and not protein’)
pdb.query(‘ protein and within 4 of ’, p3d.vector.Vector(x,y,z) )
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)
Query function using human readable syntaxe.g.: pdb.query(‘backbone and resid 5..12 and within 5 of resname FME’)
pdb.query(‘resname HOH and within 4 of resname ASP’)pdb.query(‘oxygen and not protein’)
pdb.query(‘ protein and within 4 of ’, p3d.vector.Vector(x,y,z) )
for residueName in pdb.hash[non-aa-resname]:
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)
Query function using human readable syntaxe.g.: pdb.query(‘backbone and resid 5..12 and within 5 of resname FME’)
pdb.query(‘resname HOH and within 4 of resname ASP’)pdb.query(‘oxygen and not protein’)
pdb.query(‘ protein and within 4 of ’, p3d.vector.Vector(x,y,z) )
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
List of atom objects (vectors)
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’)
pdb.query(‘resname HOH and within 4 of resname ASP’)pdb.query(‘oxygen and not protein’)
pdb.query(‘ protein and within 4 of ’, p3d.vector.Vector(x,y,z) )
for residueName in pdb.hash[non-aa-resname]: targets = pdb.query(' protein and within 4 of \ ( resname 'residueName' and oxygen )' )
Example ATP binding
Dr. C. FufezanInstitute for Biochemistry and Biotechnology of Plants (IBBP)
The ATP binding sites
Dr. C. FufezanInstitute for Biochemistry and Biotechnology of Plants (IBBP)
Adenosine-tri-phosphate
ΔG˚' = -30 kJ mol-1
40 kg / day
The ATP binding sites
non. redundant set of proteins24 binding sites
Dr. C. FufezanInstitute for Biochemistry and Biotechnology of Plants (IBBP)
The ATP binding sites
non. redundant set of proteins24 binding sites
Dr. C. FufezanInstitute for Biochemistry and Biotechnology of Plants (IBBP)
The ATP binding sites
non. redundant set of proteins24 binding sites
Dr. C. FufezanInstitute for Biochemistry and Biotechnology of Plants (IBBP)
The ATP binding sites
non. redundant set of proteins24 binding sites
Dr. C. FufezanInstitute for Biochemistry and Biotechnology of Plants (IBBP)
Dr. C. FufezanInstitute for Biochemistry and Biotechnology of Plants (IBBP)
The ATP binding site
Dr. C. FufezanInstitute for Biochemistry and Biotechnology of Plants (IBBP)
The ATP binding site
Dr. C. FufezanInstitute for Biochemistry and Biotechnology of Plants (IBBP)
The ATP binding site
+4.5
-4.5
hydropathy index
0
1
10
Observations
non. redundant set of proteins24 binding sites
Dr. C. FufezanInstitute for Biochemistry and Biotechnology of Plants (IBBP)
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
Dr. C. FufezanInstitute for Biochemistry and Biotechnology of Plants (IBBP)
Acknowledgements
Dr. C. FufezanInstitute for Biochemistry and Biotechnology of Plants (IBBP)
M. SpechtProf. Dr. M. Hippler
founding by the DFG and Alexander von Humboldt Stiftung
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