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Performance of an all-atom free energy
approach for protein structure prediction
Priya Anand, Timo Strunk, Martin Brieg, Moritz Wolf, Wolfgang Wenzel
Karlsruhe Institute of Technology, Institute of Nanotechnology, Karlsruhe, Germany
1. Introduction
5. Model Assessment
De novo prediction of protein tertiary structure on the basis of amino acid
sequence remains one of the outstanding problems in biophysical chemistry.
Protein structure prediction using homology modeling has been one of the
most popular technique to construct atomic resolution model of the target
protein. In template free modeling approach, decoy libraries are generated which
we subsequently ranked in the refinement simulations using POEM@HOME with
an all-atom free energy forcefield PFF01/02 developed in the group.
T0592
2. All-Atom Free-Energy Forcefield PFF02
• Thermodynamic hypothesis (Anfinsen): The native
•
threedimensional structure of a protein occupies the global minimum of its
free energy surface.
Locating the global minimum using stochastic optimization methods
is potentially much faster than the simulation of the folding pathway.
Table: CASP9 Predictions
Targets
T0520
T0523
T0526
T0537
T0566
T0548
T0592
T0594
T0605
T0622
3. Methodology
RMSD(Å)
2.43
3.15
2.64
4.24
2.38
3.24
2.83
1.98
1.57
3.19
(a)
TM-Score
0.840
0.714
0.816
0.600
(b)
0.715
0.786
Fig(a): PROCHECK Ramachandran
0.714
plot analysis indicated that all residues
0.796
phi/psi angle distribution was in the
core and allowed regions.
0.861
Fig(b): ERRAT plot exhibits overall
0.654
quality factor of 84.44%.
6. Free Modeling


Decoy set generations: Fragments were generated using the standard
ROSETTA fragment assembly protocol and relaxed using POEM.
Figure below shows the Energy-RMSD distribution of generated and
relaxed decoys for the FM Target T0643.
T0643
7. Refinement & Relaxation
4.Template Based Modeling
•
In Critical Assessment of Techniques for Protein Structure Prediction
(CASP9) we participated as Human expert group for TBM and FM.
•
•
T0537
Conclusions
T0520
Red: Pred.
Green: Exptal.
• PFF02 enabled us to separate inadequately built decoys from near-native
conformations in the POEM group. The computational power of POEM@HOME
allowed us rank conformations for all targets of CASP9.
• In the CASP9, TBM section we could identify native conformations very often, but
for FM most of the targets very at RMSD > 5 Å.
• POEM is still in development stage, and there is a lot of scope for improvement for
template free targets.
Modeling
disulfide
bridges:
employing distance constraints and
relaxing.
Addition
of
missing
terminal
residues:
imposed
secondary
structures prediction from PsiPred and
then relaxation
The POEM approach is implemented
into the worldwide POEM@HOME
initiative to combine the computational
power of more than 40000 PCs.
Acknowledgements
We thank the support from the BioInterfaces program.
We also thank the BOINC(http://boinc.berkeley.edu)
developers and especially our current POEM@HOME
Users for their support.
REFERENCES
[1] Verma A., and Wenzel, W. (2009) Biophys. J. Vol. 96, 3494.
Corresponding author address: Wolfgang Wenzel, Karlsruhe Institute of
Technology, Institute for Nanotechnology, Karlsruhe, Germany;
Email: [email protected], [email protected]