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Updated: Mar 26, 2026

Creating and Applying a Reference to Facilitate the Discussion and Classification of Proteins in a Diverse Group
Published on: August 16, 2017
Structural homology guided alignment of cysteine rich proteins
Thomas M A Shafee1, Andrew J Robinson2, Nicole van der Weerden1
1Department of Biochemistry, La Trobe Institute of Molecular Sciences, La Trobe University, Melbourne, 3086 Australia.
Background:
Cysteine rich protein families are notoriously difficult to align due to low sequence identity and frequent insertions and deletions.
Results:
Here we present an alignment method that ensures homologous cysteines align by assigning a unique 10 amino acid barcode to those identified as structurally homologous by the DALI webserver. The free inter-cysteine regions of the barcoded sequences can then be aligned using any standard algorithm. Finally the barcodes are replaced with the original columns to yield an alignment which requires the minimum of manual refinement.
Conclusions:
Using structural homology information to constrain sequence alignments allows the alignment of highly divergent, repetitive sequences that are poorly dealt with by existing algorithms. Tools are provided to perform this method online using the CysBar web-tool (http://CysBar.science.latrobe.edu.au) and offline (python script available from http://github.com/ts404/CysBar).
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