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Creating and Applying a Reference to Facilitate the Discussion and Classification of Proteins in a Diverse Group
Published on: August 16, 2017
Protein sequence alignment with family-specific amino acid similarity matrices
1Cancer Research Center, Department of Epidemiology and Biostatistics, University at Albany, State University of New York, One Discovery Drive, Rensselaer, NY, USA 12144. ikuznetsov@albany.edu.
BMC Research Notes
|August 18, 2011
Summary
Optimized protein sequence alignment uses family-specific scoring matrices to enhance homologous sequence alignment quality. Fold-specific matrices offer minor improvements for proteins with similar structures but different evolutionary origins.
Area of Science:
- Bioinformatics
- Computational Biology
- Structural Biology
Background:
- Dynamic programming is essential for sequence alignment, but its accuracy relies heavily on the scoring function.
- Selecting optimal scoring functions is crucial for effective sequence comparison.
- This study focuses on developing optimized protein family- and fold-specific scoring functions for global alignment.
Purpose of the Study:
- To develop and evaluate protein family- and fold-specific scoring functions for sequence alignment.
- To compare the performance of general-purpose matrices against specialized ones.
- To introduce an adaptive alignment procedure for selecting optimal matrices and gap penalties.
Main Methods:
- Utilized a quantitative statistical framework based on structural superposition of homologous and analogous proteins.
- Evaluated general-purpose amino acid similarity matrices on specific protein families and folds.
- Derived and compared family-specific and fold-specific matrices.
- Developed an adaptive alignment procedure for automatic matrix and gap penalty selection.
Main Results:
- Family-specific similarity matrices significantly improve the alignment quality of homologous sequences.
- General-purpose matrices perform less effectively than specialized matrices for specific protein families.
- Fold-specific matrices provide only marginal improvements for proteins with similar structures but divergent evolutionary histories.
Conclusions:
- Family-specific matrices represent a substantial advancement for homologous sequence alignment.
- Fold-specific matrices offer limited benefits for non-homologous proteins with similar folds.
- Derived family-specific matrices and optimized gap penalties are publicly available for use.
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