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Multiple structure alignment with msTALI.

Shealy P, Valafar H - BMC Bioinformatics (2012)

Bottom Line: Although multiple structure alignment algorithms can potentially be applied to a number of problems, they have primarily been used for protein core identification.We also demonstrate success at building a database of protein cores using 341 randomly selected CATH domains and highlight the contribution of msTALI compared to the CATH classifications.In addition to its performance on standard comparison databases, it utilizes clear, informative features, allowing further customization for domain-specific applications.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Computer Science and Engineering, University of South Carolina, Columbia, SC 29208, USA.

ABSTRACT

Background: Multiple structure alignments have received increasing attention in recent years as an alternative to multiple sequence alignments. Although multiple structure alignment algorithms can potentially be applied to a number of problems, they have primarily been used for protein core identification. A method that is capable of solving a variety of problems using structure comparison is still absent. Here we introduce a program msTALI for aligning multiple protein structures. Our algorithm uses several informative features to guide its alignments: torsion angles, backbone Cα atom positions, secondary structure, residue type, surface accessibility, and properties of nearby atoms. The algorithm allows the user to weight the types of information used to generate the alignment, which expands its utility to a wide variety of problems.

Results: msTALI exhibits competitive results on 824 families from the Homstrad and SABmark databases when compared to Matt and Mustang. We also demonstrate success at building a database of protein cores using 341 randomly selected CATH domains and highlight the contribution of msTALI compared to the CATH classifications. Finally, we present an example applying msTALI to the problem of detecting hinges in a protein undergoing rigid-body motion.

Conclusions: msTALI is an effective algorithm for multiple structure alignment. In addition to its performance on standard comparison databases, it utilizes clear, informative features, allowing further customization for domain-specific applications. The C++ source code for msTALI is available for Linux on the web at http://ifestos.cse.sc.edu/mstali.

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Related in: MedlinePlus

A superposition of three zinc finger domains, residues 479–525. 1KTQ is shown in red, 2KTQ is green, 3KTQ is blue. An additional hinge region, residues 514–517, is shown in gray.
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Figure 2: A superposition of three zinc finger domains, residues 479–525. 1KTQ is shown in red, 2KTQ is green, 3KTQ is blue. An additional hinge region, residues 514–517, is shown in gray.

Mentions: In contrast, results of msTALI alignment are far more informative as illustrated in Table3 (the complete alignment is in Additional file 1: Table S3). Based on results shown in this table, all structurally conserved regions across all three structures are identified. In addition to the conserved structural regions, the hinge points that accommodate conformational changes can be identified by observing per-residue score that is provided by msTALI. The per-residue score provides information regarding the structural conservation of each residue using the final alignment information. Residues with significant deviations in their scores (more than 3σ in this report) can be identified as exact location of structural disagreement. Figure1 illustrates the hinge points of motion that are identified for the region between residues 469 and 529 (Additional file 1: Figure S1 illustrates the results for the entire alignment). Residues corresponding to hinges are highlighted in the msTALI alignments shown in Table3. Two points of motion for the thumb domain are identified by msTALI:residues G479 and A525 neatly delineate the 12° rotation of the H1 and H2 helices. The three structures exhibit a backbone RMSD of more than 5 Å over the backbone atoms of residues 479–525 after superimposing the remainder of the proteins. The high RMSD indicates the significant local structural change that has occurred over the three proteins. To validate the conservation of local structure, the RMSD of the same region can be obtained by superimposing only the local region (residues 479–525), as shown in Figure2. This exercise yields an RMSD of less than 1.3 Å, which indicates the conservation of the local region as indicated by msTALI. Our analysis has also identified two additional hinge regions corresponding to residues T514 and A517. This region has been illustrated in gray in Figure2. The original work also notes that the complete thumb domain undergoes motion, but the delineating residues are not identified by msTALI.


Multiple structure alignment with msTALI.

Shealy P, Valafar H - BMC Bioinformatics (2012)

A superposition of three zinc finger domains, residues 479–525. 1KTQ is shown in red, 2KTQ is green, 3KTQ is blue. An additional hinge region, residues 514–517, is shown in gray.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3473313&req=5

Figure 2: A superposition of three zinc finger domains, residues 479–525. 1KTQ is shown in red, 2KTQ is green, 3KTQ is blue. An additional hinge region, residues 514–517, is shown in gray.
Mentions: In contrast, results of msTALI alignment are far more informative as illustrated in Table3 (the complete alignment is in Additional file 1: Table S3). Based on results shown in this table, all structurally conserved regions across all three structures are identified. In addition to the conserved structural regions, the hinge points that accommodate conformational changes can be identified by observing per-residue score that is provided by msTALI. The per-residue score provides information regarding the structural conservation of each residue using the final alignment information. Residues with significant deviations in their scores (more than 3σ in this report) can be identified as exact location of structural disagreement. Figure1 illustrates the hinge points of motion that are identified for the region between residues 469 and 529 (Additional file 1: Figure S1 illustrates the results for the entire alignment). Residues corresponding to hinges are highlighted in the msTALI alignments shown in Table3. Two points of motion for the thumb domain are identified by msTALI:residues G479 and A525 neatly delineate the 12° rotation of the H1 and H2 helices. The three structures exhibit a backbone RMSD of more than 5 Å over the backbone atoms of residues 479–525 after superimposing the remainder of the proteins. The high RMSD indicates the significant local structural change that has occurred over the three proteins. To validate the conservation of local structure, the RMSD of the same region can be obtained by superimposing only the local region (residues 479–525), as shown in Figure2. This exercise yields an RMSD of less than 1.3 Å, which indicates the conservation of the local region as indicated by msTALI. Our analysis has also identified two additional hinge regions corresponding to residues T514 and A517. This region has been illustrated in gray in Figure2. The original work also notes that the complete thumb domain undergoes motion, but the delineating residues are not identified by msTALI.

Bottom Line: Although multiple structure alignment algorithms can potentially be applied to a number of problems, they have primarily been used for protein core identification.We also demonstrate success at building a database of protein cores using 341 randomly selected CATH domains and highlight the contribution of msTALI compared to the CATH classifications.In addition to its performance on standard comparison databases, it utilizes clear, informative features, allowing further customization for domain-specific applications.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Computer Science and Engineering, University of South Carolina, Columbia, SC 29208, USA.

ABSTRACT

Background: Multiple structure alignments have received increasing attention in recent years as an alternative to multiple sequence alignments. Although multiple structure alignment algorithms can potentially be applied to a number of problems, they have primarily been used for protein core identification. A method that is capable of solving a variety of problems using structure comparison is still absent. Here we introduce a program msTALI for aligning multiple protein structures. Our algorithm uses several informative features to guide its alignments: torsion angles, backbone Cα atom positions, secondary structure, residue type, surface accessibility, and properties of nearby atoms. The algorithm allows the user to weight the types of information used to generate the alignment, which expands its utility to a wide variety of problems.

Results: msTALI exhibits competitive results on 824 families from the Homstrad and SABmark databases when compared to Matt and Mustang. We also demonstrate success at building a database of protein cores using 341 randomly selected CATH domains and highlight the contribution of msTALI compared to the CATH classifications. Finally, we present an example applying msTALI to the problem of detecting hinges in a protein undergoing rigid-body motion.

Conclusions: msTALI is an effective algorithm for multiple structure alignment. In addition to its performance on standard comparison databases, it utilizes clear, informative features, allowing further customization for domain-specific applications. The C++ source code for msTALI is available for Linux on the web at http://ifestos.cse.sc.edu/mstali.

Show MeSH
Related in: MedlinePlus