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Multiple structural alignment for distantly related all beta structures using TOPS pattern discovery and simulated
A Williams1, D R Gilbert, D R Westhead
1School of Biochemistry and Molecular Biology, University of Leeds, Leeds LS2 9JT.
Protein Engineering
|February 26, 2004
Summary
Topsalign is a novel method for aligning diverse protein structures, even with low sequence identity. It effectively uses topological descriptions and pattern discovery to create accurate multiple structure alignments and superpositions.
Area of Science:
- Computational Biology
- Structural Bioinformatics
- Protein Structure Analysis
Background:
- Protein superfolds share common structural scaffolds but exhibit low sequence identity and functional diversity.
- Significant structural variations can exist within superfolds, challenging traditional alignment methods.
Purpose of the Study:
- To introduce Topsalign, a new method for structurally aligning diverse protein structures.
- To evaluate Topsalign's performance against established methods on challenging protein superfamilies.
Main Methods:
- Topsalign utilizes topological protein descriptions and a pattern discovery algorithm to identify equivalent secondary structure elements.
- An initial multiple structure alignment is generated, followed by optimization using simulated annealing.
- The method outputs a multiple structure-based sequence alignment and a 3D superposition of protein structures.
Main Results:
- Topsalign successfully aligned diverse protein structures from three superfolds: beta-jelly roll, TIM (alpha/beta) barrel, and OB fold.
- The method demonstrated superior performance compared to existing techniques, particularly for highly diverse structures.
- Topsalign effectively aligned TIM (alpha/beta) barrel superfamilies, despite the pattern discovery focusing on beta strands.
Conclusions:
- Topsalign provides an effective approach for structural alignment of proteins with low sequence identity and high structural diversity.
- The method's ability to handle mixed secondary structure elements (alpha-helices and beta-strands) enhances its applicability.