User:Eric Martz/Sandbox 11

From Proteopedia

Revision as of 14:22, 4 October 2010

Proposed page title: Structural Alignment Tools
Structural alignment refers to the alignment, in three dimensions, between two or more molecular models. In the case of proteins, this is usually performed without reference to the sequences of the proteins.

Wikipedia offers a list of structural alignment software packages and an overview of structural alignment.

Structural Alignment Servers

Alphabetical, by server name:

CE

The Combinatorial Extension structural alignment server.

• Server: CE Home Page.
• Publication (1998)^[1]
• N.B. Database of structure neighbors has not been updated since 2004. Java applet for viewing results is not working in Sept. 2010. Finding structure neighbors from the entire PDB database ("ALL") appears to have been broken since 2001.
• Rigid alignment: ONLY (according to FATCAT^[2])
• Structure-based sequence alignment: YES.

DALI

• Rigid alignment: ONLY (according to FATCAT^[2])

FATCAT

• Server: fatcat.burnham.org Flexible structure AlignmenT by Chaining AFPs (Aligned Fragment Pairs) with Twists (FATCAT)
• Publication (2003)^[2] "... the FATCAT algorithm achieves more accurate structure alignments than current methods, while at the same time introducing fewer hinges."
• Help on server: YES with snapshots; some context-sensitive help.
• Does alignment involve sequence comparison? UNCLEAR.
• Rigid alignment: YES (optional)
• Flexible alignment: YES (optional)
• Structure neighbors (pre-calculated): YES
• Pairwise alignment including uploaded models: YES
• Visualization: Jmol or Chime. See Special features.
• Color by deviation: NO. (Colors identify twist/hinge boundaries.)
• Offered by RCSB? YES
• Special features: Produces a morph between the two aligned chains (at the link "Interpolating between ..."). Produces a sequence alignment. Offers a RasMol script to color each rigid segment distinctly (separated by twists/hinges).

Notes from the publication: With 10 "difficult examples"^[3] FATCAT produced results comparable (length, RMSD) to the rigid alignment servers DALI, VAST, CE with no twists in 8 cases. This shows that FATCAT is not biased to introduce twists (hinges). Hinges were introduced in two of the difficult cases, producing arguably better alignments. In a comparison with FlexProt^[4], FATCAT obtained similar RMSD's and aligned lengths with fewer twists (hinges).

FlexProt

• Server: FlexProt.
• Publication (2002)^[5]
• Rigid alignment: YES (Results include alignment for 0 hinges, but only a well-aligning subset of residues are aligned.)
• Flexible alignment: YES (Results are given for various numbers of hinges.)
• Visualization: NONE (You can download PDB files.)
• Ligands: Discarded.
• Special features: Assigns a distinct chain name to each rigid segment separated by a hinge, facilitating informative coloring.

Note: FATCAT provides evidence that it out-performs FlexProt.

MAMMOTH

• Server: mammoth MAMMOTH (MAtching Molecular Models Obtained from THeory)
• Publication (2002)^[6]
• Help on server: Little or none.
• Does alignment involve sequence comparison? NO: They state that this is a "sequence-independent structural alignment".
• Rigid alignment: YES.
• Flexible alignment: NO.
• Multiple alignment: YES.
• Structure neighbors (pre-calculated): NO.
• Pairwise alignment including uploaded models: YES
• Visualization: None (you can download a PDB file and a RasMol script. PDB file lacks MODEL/ENDMDL delimiters. PDB file has no chain names. There is a PDB file with chains A and B in the downloadable file rasmol.tcl but this is not a Jmol-ready file.)
• Color by deviation: NO.
• Offered by RCSB? YES

TM-Align

• Server: TM-align
• Publication (2005)^[6]
• Help on server: A little.
• Does alignment involve sequence comparison? UNCLEAR.
• Rigid alignment: YES.
• Flexible alignment: NO.
• Multiple alignment: You can download the software to run on linux.
• Structure neighbors (pre-calculated): NO.
• Pairwise alignment including uploaded models: YES
• Visualization: None (you can download a script for RasMol that contains PDB coordinates. PDB file lacks MODEL/ENDMDL delimiters. PDB file has no chain names. File does not run as a script in Jmol due to REMARK lines that are not legal Jmol commands.)
• Color by deviation: NO.
• Offered by RCSB? YES

TopMatch

• Server: TopMatch
• Publications (both 2008)^[7][8]
• Help on server: YES.
• Does alignment involve sequence comparison? UNCLEAR.
• Rigid alignment: YES.
• Flexible alignment: NO.
• Multiple alignment: NO.
• Structure neighbors (pre-calculated): NO.
• Pairwise alignment including uploaded models: YES
• Visualization: Jmol.
• Color by deviation: NO.
• Offered by RCSB? YES
• Special features: You can download the aligned target PDB file (in a separate file from the query PDB file). A PyMOL script is also available.

VAST

Rigid alignment: ONLY (according to FATCAT^[2])

Structural Alignment Software

Calculate Structure Alignment

This is a java program (java web start) offered by the U.S. PDB. At the PDB website, look for the box of Tools on the left hand side, and click on Compare Structures. You will then get a form where you can enter two PDB codes (or upload two PDB files), optionally with a sequence range for each. Alternatively, with the Database Search option, you can enter a single PDB code (or upload a PDB file), and find structure neighbors. On the right is a link "Align custom files (Launches a Java Web Start application)", which starts the Calculate Structure Alignment java software. This package offers java implementations of the CE and FATCAT (you can choose rigid or flexible) algorithms (see above).

Examples

Example Requiring Flexibility

This example requires flexibility for a good alignment: 2bbm:A vs. 1cfc:A. Length: 148. 97% sequence identity (145/148), 99% similar. These files contain calmodulin. In 2bbm (Drosophila), the two calcium-binding domains are wrapped around a peptide. In 1cfc (Xenopus), there is no calcium and no peptide, and the linker between the two domains is flexible.

• CE:
  • 4.8 Å RMSD.
  • 38.5% sequence identity in structure-based sequence alignment. Aligned/gap positions = 109/47.
  • Uses old, unremediated PDB files (1cfc has no chain A).
• FATCAT:
  • 5 hinges(twists): 140 residues aligned, RMSD 2.08 Å.
• FlexProt:
  • 0 hinges: 49 residues aligned, RMSD 2.94 Å.
  • 1 hinge: 84 residues aligned, RMSD 2.97 Å.
  • 2 hinges: 102 residues aligned, RMSD 2.82 Å.
  • 3 hinges: 118 residues aligned, RMSD 2.60 Å.
  • 4 hinges: 134 residues aligned, RMSD 2.62 Å.

Example for Rigid Alignment

1fsz is the bacterial cell division protein FtsZ, length 334 residues with coordinates (372 in crystallized protein). It has structural similarity to mammalian tubulin found in 1tub chain A, length 440.

CE

• 3.2 Å RMSD for 305 residues. The structural alignment has 96 unaligned "gap" residues: one large gap of ~30 residues, and ten smaller gaps of 8 residues or less.
• 12.5% sequence identity.

FATCAT

• 3.02 Å RMSD RIGID alignment includes 298 residues.
• FLEXIBLE alignment introduced ZERO twists (hinges), so gave the same result as the rigid alignment.
• The structure-based sequence alignment has many gaps, looking similar to that generated by CE.

MAMMOTH

• 4.0 Å (?) with 298 aligned residues (?) (Labeling in results is unclear.)
• Structure-based sequence alignment is displayed.

TM-Align

• 3.42 Å for 312 aligned residues.
• Structure-based sequence alignment is displayed.

TopMatch

• Error # 1063, no explanation. No structures displayed in Jmol.
• 3.1 Å RMSD. Alignment includes 251 residues. Sequence identity in the aligned regions is 12%.
• Structure-based sequence alignment is displayed.
• Tried the example requiring flexibility (above) as a second case. A 40 residue subdomain was aligned with RMSD 1.8 Å, and the alignment was displayed in Jmol with no error.

References

1. ↑ Shindyalov IN, Bourne PE. Protein structure alignment by incremental combinatorial extension (CE) of the optimal path. Protein Eng. 1998 Sep;11(9):739-47. PMID:9796821
2. ↑ ^{2.0 2.1 2.2 2.3} Ye Y, Godzik A. Flexible structure alignment by chaining aligned fragment pairs allowing twists. Bioinformatics. 2003 Oct;19 Suppl 2:ii246-55. PMID:14534198
3. ↑ Fischer,D., Elofsson,A., Rice,D. and Eisenberg,D. (1996) Assessing the performance of fold recognition methods by means of a comprehensive benchmark. In Pacific Symposium on Biocomputing. pp. 300–318.
4. ↑ Shatsky M, Nussinov R, Wolfson HJ. Flexible protein alignment and hinge detection. Proteins. 2002 Aug 1;48(2):242-56. PMID:12112693 doi:10.1002/prot.10100
5. ↑ Shatsky M, Nussinov R, Wolfson HJ. Flexible protein alignment and hinge detection. Proteins. 2002 Aug 1;48(2):242-56. PMID:12112693 doi:10.1002/prot.10100
6. ↑ ^{6.0 6.1} Ortiz AR, Strauss CE, Olmea O. MAMMOTH (matching molecular models obtained from theory): an automated method for model comparison. Protein Sci. 2002 Nov;11(11):2606-21. PMID:12381844 doi:10.1110/ps.0215902
7. ↑ Sippl MJ, Wiederstein M. A note on difficult structure alignment problems. Bioinformatics. 2008 Feb 1;24(3):426-7. Epub 2008 Jan 2. PMID:18174182 doi:10.1093/bioinformatics/btm622
8. ↑ Sippl MJ. On distance and similarity in fold space. Bioinformatics. 2008 Mar 15;24(6):872-3. Epub 2008 Jan 28. PMID:18227113 doi:10.1093/bioinformatics/btn040