User:Eric Martz/Sandbox 11

From Proteopedia

proteopedia linkproteopedia link

Proposed page title: Structural Alignment Tools

Contents 1 Structural Alignment Servers 1.1 CE 1.2 DALI 1.3 FATCAT 1.4 FlexProt 1.5 VAST 2 Structural Alignment Software 3 Examples 3.1 Example Requiring Flexibility 3.2 Example for Rigid Alignment 4 References

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.

VAST

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

Structural Alignment Software

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.

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