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TOPS++FATCAT: fast flexible structural alignment using constraints derived from TOPS+ Strings Model.

Veeramalai M, Ye Y, Godzik A - BMC Bioinformatics (2008)

Bottom Line: Such intuitions could help speed up similarity searches and make it easier to understand the results of such analyses.For beta-rich proteins its accuracy is better than FATCAT, because the TOPS+ strings models contains important information of the parallel and anti-parallel hydrogen-bond patterns between the beta-strand SSEs (Secondary Structural Elements).We show that the TOPS++FATCAT errors, rare as they are, can be clearly linked to oversimplifications of the TOPS diagrams and can be corrected by the development of more precise secondary structure element definitions.

View Article: PubMed Central - HTML - PubMed

Affiliation: Joint Center for Molecular Modeling, Burnham Institute for Medical Research, La Jolla, CA 92037, USA. mallikav@burnham.org

ABSTRACT

Background: Protein structure analysis and comparison are major challenges in structural bioinformatics. Despite the existence of many tools and algorithms, very few of them have managed to capture the intuitive understanding of protein structures developed in structural biology, especially in the context of rapid database searches. Such intuitions could help speed up similarity searches and make it easier to understand the results of such analyses.

Results: We developed a TOPS++FATCAT algorithm that uses an intuitive description of the proteins' structures as captured in the popular TOPS diagrams to limit the search space of the aligned fragment pairs (AFPs) in the flexible alignment of protein structures performed by the FATCAT algorithm. The TOPS++FATCAT algorithm is faster than FATCAT by more than an order of magnitude with a minimal cost in classification and alignment accuracy. For beta-rich proteins its accuracy is better than FATCAT, because the TOPS+ strings models contains important information of the parallel and anti-parallel hydrogen-bond patterns between the beta-strand SSEs (Secondary Structural Elements). We show that the TOPS++FATCAT errors, rare as they are, can be clearly linked to oversimplifications of the TOPS diagrams and can be corrected by the development of more precise secondary structure element definitions.

Software availability: The benchmark analysis results and the compressed archive of the TOPS++FATCAT program for Linux platform can be downloaded from the following web site: http://fatcat.burnham.org/TOPS/ CONCLUSION: TOPS++FATCAT provides FATCAT accuracy and insights into protein structural changes at a speed comparable to sequence alignments, opening up a possibility of interactive protein structure similarity searches.

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(a) TOPS+ graph model, (b) TOPS+ strings model, and (c) TOPS+ strings matches between Dihydropteridine reductase from rat (1dhr) and human (1hdr). All the conserved TOPS+ strings elements are shown with pink arrows. Dotted arrows indicate matched helices and strands, plain arrows indicate matched loops, and arrows with double lines indicate matched ligand-interacting loops.
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Figure 3: (a) TOPS+ graph model, (b) TOPS+ strings model, and (c) TOPS+ strings matches between Dihydropteridine reductase from rat (1dhr) and human (1hdr). All the conserved TOPS+ strings elements are shown with pink arrows. Dotted arrows indicate matched helices and strands, plain arrows indicate matched loops, and arrows with double lines indicate matched ligand-interacting loops.

Mentions: The TOPS model was further enhanced to incorporate features such as protein-ligand interaction information and more detailed secondary structural segment information. This enhanced model is called TOPS+ model (see Figure 3a). This TOPS+ model can be described formally in a TOPS+ strings language (Figure 3b) at a reduced linear level. The enhanced TOPS+ strings models can be used in fast string-based structure matching and comparison, at the same time avoiding issues of NP-completeness associated with graph alignments.


TOPS++FATCAT: fast flexible structural alignment using constraints derived from TOPS+ Strings Model.

Veeramalai M, Ye Y, Godzik A - BMC Bioinformatics (2008)

(a) TOPS+ graph model, (b) TOPS+ strings model, and (c) TOPS+ strings matches between Dihydropteridine reductase from rat (1dhr) and human (1hdr). All the conserved TOPS+ strings elements are shown with pink arrows. Dotted arrows indicate matched helices and strands, plain arrows indicate matched loops, and arrows with double lines indicate matched ligand-interacting loops.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2553092&req=5

Figure 3: (a) TOPS+ graph model, (b) TOPS+ strings model, and (c) TOPS+ strings matches between Dihydropteridine reductase from rat (1dhr) and human (1hdr). All the conserved TOPS+ strings elements are shown with pink arrows. Dotted arrows indicate matched helices and strands, plain arrows indicate matched loops, and arrows with double lines indicate matched ligand-interacting loops.
Mentions: The TOPS model was further enhanced to incorporate features such as protein-ligand interaction information and more detailed secondary structural segment information. This enhanced model is called TOPS+ model (see Figure 3a). This TOPS+ model can be described formally in a TOPS+ strings language (Figure 3b) at a reduced linear level. The enhanced TOPS+ strings models can be used in fast string-based structure matching and comparison, at the same time avoiding issues of NP-completeness associated with graph alignments.

Bottom Line: Such intuitions could help speed up similarity searches and make it easier to understand the results of such analyses.For beta-rich proteins its accuracy is better than FATCAT, because the TOPS+ strings models contains important information of the parallel and anti-parallel hydrogen-bond patterns between the beta-strand SSEs (Secondary Structural Elements).We show that the TOPS++FATCAT errors, rare as they are, can be clearly linked to oversimplifications of the TOPS diagrams and can be corrected by the development of more precise secondary structure element definitions.

View Article: PubMed Central - HTML - PubMed

Affiliation: Joint Center for Molecular Modeling, Burnham Institute for Medical Research, La Jolla, CA 92037, USA. mallikav@burnham.org

ABSTRACT

Background: Protein structure analysis and comparison are major challenges in structural bioinformatics. Despite the existence of many tools and algorithms, very few of them have managed to capture the intuitive understanding of protein structures developed in structural biology, especially in the context of rapid database searches. Such intuitions could help speed up similarity searches and make it easier to understand the results of such analyses.

Results: We developed a TOPS++FATCAT algorithm that uses an intuitive description of the proteins' structures as captured in the popular TOPS diagrams to limit the search space of the aligned fragment pairs (AFPs) in the flexible alignment of protein structures performed by the FATCAT algorithm. The TOPS++FATCAT algorithm is faster than FATCAT by more than an order of magnitude with a minimal cost in classification and alignment accuracy. For beta-rich proteins its accuracy is better than FATCAT, because the TOPS+ strings models contains important information of the parallel and anti-parallel hydrogen-bond patterns between the beta-strand SSEs (Secondary Structural Elements). We show that the TOPS++FATCAT errors, rare as they are, can be clearly linked to oversimplifications of the TOPS diagrams and can be corrected by the development of more precise secondary structure element definitions.

Software availability: The benchmark analysis results and the compressed archive of the TOPS++FATCAT program for Linux platform can be downloaded from the following web site: http://fatcat.burnham.org/TOPS/ CONCLUSION: TOPS++FATCAT provides FATCAT accuracy and insights into protein structural changes at a speed comparable to sequence alignments, opening up a possibility of interactive protein structure similarity searches.

Show MeSH