Evaluate new Secondary-structure Specific aminoacid exchange matrices in the Premium-Praline alignment programme

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About Evaluate new Secondary-structure Specific aminoacid exchange matrices in the Premium-Praline alignment programme


In a recent project by Marlies van der Wees, a new set of secondary-structure (SS) specific aminoacid exchange matrices was calculated. The pre-existing SS specific matrices were determined by Luthy et al (1991)[1] based on only a 500 sequences from a few protein families. The new matrices make better use of the growing number of protein structures available from the PDB structure database (www.rcsb.org/pdb) which currently holds well over 55.000 structures, compared to less than 2.000 in 1993.

A useful application of these matrices is to evaluate their added value in the Premium-Praline alignment program [2], that has recently been expanded to be secondary-structure aware. This means that, based on predicted secondary structure information for input sequences, during the DP alignment steps alternate exchange matrices are chosen for different positions in the sequences.

Using existing execution and analysis scripts, the project entails the re-evaluation of the performance of Premium-Praline using the new matrices.

In addition, the new matrices were determined based on the secondary structure definition of only a single sequence in the references alignment (BLOCKS database) used. Further refinement of the SS specific matrices is possible by incorporating all known structures and SS assignments, and using only SS conserved positions. These refined matrices will also be tested for alignment efficacy using Premium Praline.

Depending on the numbers of sites involved, it might even be feasible to extract matrices for positions with heterogeneous (non-conserved) SS assignments. To test these, the Praline alignment framework would have to be expanded to incorporate the additional 'classes' of SS assignment and corresponding matrices.

Related project:

Re-calculate secondary-structure specific aminoacid exchange matrices (Marlies van der Wees)


  1. Lüthy et al 1991 Lüthy R, McLachlan AD, Eisenberg D. Secondary structure-based profiles: use of structure-conserving scoring tables in searching protein sequence databases for structural similarities. Proteins. 1991;10:229-39 pdf
  2. Pirovano et al 2008 Pirovano W, Feenstra KA, Heringa J. PRALINETM: a strategy for improved multiple alignment of transmembrane proteins. Bioinformatics. 2008 24:492-7.