Beta-Alpha-Beta Builder
What is Beta-Alpha-Beta Builder?
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The Beta-Alpha-Beta Builder is a program that adds alpha-helices onto a beta-sheet. Both loops of each helices have the constraint of beeing connected somewhere on the beta-sheet. The program first backtracks on loop and helix fragments from the Protein Data Bank to build each beta-alpha-beta units individually, then backtracks on these units to find non-clashing helix pairs.
The featured beta-sheet is from Baker's Top7 de novo protein (PDB code 1QYS).
The result of the execution should give you
53 solutions, i.e. PDB files (named '1qys-00001.pdb'...). The loop and helix
databases has been compiled from the annotations of the
program DSSP [4] on the culled PDB [7].
The program's parameter needs further explanations:
- The last parameter (here 1.5) is the output structure cache and
it's value is in Angstroms. Each time a complete 3D structure is
generated it is compared to all the ones in the structure cache. If it
is different enough from all these structures then it is outputted as
a solution and the new structure is put in the cache with the
others. This is to prevent from having thousands of similar solutions,
as any good backtracking algorithm can yield!
- The second to last parameter (here 1.0) is the closure RMSD. When
a complete loop-helix-loop fragment is attached to one end on the
first beta-sheet anchor the distance at the other end of the fragment
to the second beta-sheet anchor is measured. A perfect match would
have a RMSD of zero. RMSDs higher than the specified value are
considered too big for the main-chain closure at the loop/beta-sheet
anchor.
- The third to last parameter (here 5.0) is the minimum RMSD between
instances in the helix backtrack set. This value is in Angstroms. In
order for a new 3D structure of an alpha-helix to be part of the
backtrack it must be at least this value apart from all the previously
loaded helices. This is to prevent from having too similar helix
structures in the backtrack sets that would end up generating similar
3D structures. Lower values increases the database loading time and
yield bigger backtrack tree. Start with high values like 5.0 Angstroms
and work your way downward to acceptable database loading time.
- The fourth to last parameter (here 1.0) is the minimum RMSD between
instances in the loop backtrack set. This value is in Angstroms. In
order for a new 3D structure of a loop to be part of the
backtrack it must be at least this value apart from all the previously
loaded loops. This is to prevent from having too similar loop
structures in the backtrack sets that would end up generating similar
3D structures. Lower values increases the database loading time and
yield bigger backtrack tree. Start with high values like 1.0 Angstroms
and work your way downward to acceptable database loading time.
- The fifth to last parameter (here ./helices.25.dat) is the file
name of the helices database.
- The sixth to last parameter (here ./loops.25.dat) is the file
name of the loops database.
- The seventh to last parameter (here ./1qys.sheet.pdb) is a PDB
file which holds the 3D structure of the beta-sheet to add helices
on.
- The eighth to last parameter (here ./baker.helix.bab) is a
descriptor file which explicits the beta-alpha-beta residue sequences
and also the beta-alpha-beta residue ranges. Notice that the file ends
with two LOOP/HELIX/LOOP lines and that the last residue of a fragment
is also the first residue of the next consecutive fragment.
The following 3D structures have been generated with this command:
./bab.exe ./baker.helix.bab ./1qys.sheet.pdb ./loops.25.dat ./helices.25.dat 1.0 5.0 1.0 1.5
Figure 1: Fifty-three 3-D models for
the two beta-alpha-beta units in Baker's Top7 protein (PDB code
1QYS). All models are aligned on the beta-sheet to show the
conformational sampling. The models are at least 1.5 Angstroms from
each other. Colors are from blue for N-terminus to red for
C-terminus. Notice that all beta-alpha-beta units are all "on top" of
the beta-sheet, in accord with the right-handedness of connections in
proteins. Figures were produced using RasMol [1].
A) Top view.
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B) Bottom view.
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A) Front view.
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B) Back view.
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A) Side view #1.
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B) Side view #2.
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Since the positioning of the alpha-helices on the beta-sheet is a
purely geometrical procedure we are left with 3D structures in which
the hydrophobic moments of the alpha-helices may not be optimized. We
have made a program that optimizes the HFS score [9][10], therefore
the hydrophobic moments, by rotating the alpha-helices on their main
axis to the best of the HFS score. The program takes for input a PDB
file and will optimize any helices that are described in the proper
HELIX PDB records. The original file is backed-up (with a .bak suffix)
then replaced by the optimized helices.
- Step 1:Download the LINUX binary version of the Helix Optimizer.
- Step 2: execute:
./optHelix.exe 1pou.pdb
The result of the execution on the first model in the PDB file 1POU:
Loading PDB file: `1pou.pdb'
Initial energy: -3.70295
Final energy: -4.10463
Helix 1 has rotated +29 degrees
Helix 2 has rotated -2 degrees
Helix 3 has rotated -23 degrees
Helix 4 has rotated -8 degrees
Need to add some beta-turns or some loops into your 3D models? use addFrag! It will select the best fragment from the PDB to bridge the gap between any pair of residues. It does not optimize the loop closure afterwards, though, but the selected turn/loop could be a good starting configuration for a subsequent minimization.
WARNING: The PDB file will be replaced with a version that includes the turns/loops; make a copy of it before launching addFrag. To add turns, use -T; to add loops use -L instead. To zap the PDB file when a fragment cannot be inserted satisfactorily use -Z 1.5, as in:
./addFrag.exe -T -Z 1.5 baker.all.bab 1qys.sheet.noturn.pdb loops.25.dat
Lower values to Z will produce better chain closure but the probability to satisfy it will drop accordingly.
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[1] R. A. Sayle, E. J. Milner-White, Rasmol: Biomolecular graphics for all, Trends Biol. Sci. 20 (1995) 374-376.
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[2] P. J. Kraulis, Molscript: a program to produce both detailed and schematic plots of protein structures, Journal of Applied Crystallography 24 (1991) 946-950.
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[3] E. A. Merritt, D. J. Bacon, Raster3D: Photorealistic Molecular Graphics, Methods in Enzymology 277 (1997) 505-524.
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[4] W. Kabsch, C. Sander, Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features, Biopolymers 22 (1983) 2577-2637.
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[5] H. M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T. N. Bhat, H. Weissig, I. N. Shindyalov, P. E. Bourne, The Protein Data Bank, Nucl. Acids Res. 28 (2000) 235-242.
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[6] B. Kuhlman, G. Dantas, G. C. Ireton, G. Varani, B. L. Stoddard, D. Baker, Design of a novel globular protein fold with atomic-level accuracy, Science 302 (2003) 1364-1368.
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[7] G. Wang, R. L. Dunbrack Jr, PISCES: a protein sequence culling server, Bioinformatics 19 (2003) 1589-1591.
The X-Ray resolution is 2.0 A, R-Factor at 0.25 and no more than 25% sequence identity. As of the 7th Feb. 2004 it contained 1966 chains.
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[8] M. Parisien, F. Major, A new catalog of protein beta-sheets, Unpublished. See Beta-Spider.
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[9] Huang, E. S., Subbiah, S. & Levitt, M. Recognizing native folds by the arrangement of hydrophobic and polar residues. J. Mol. Biol. 252 (1995) 709-720.
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[10] Huang, E. S., Subbiah, S., Tsai, J. & Levitt, M. Using a hydrophobic contact potential to evaluate native and near-native folds generated by molecular dynamics simulations. J. Mol. Biol. 257 (1996) 716-725.
Marc Parisien
Created: 19/10/2004 Last update: 19/10/2004
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