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Within the twilight zone: a sensitive profile-profile comparison tool based on information theory
1Department of Structural Biology, Fairchild Bldg. D-109, Stanford University, CA 94305, USA. golan@cs.cornell.edu
Journal of Molecular Biology
|February 6, 2002
Summary
This study introduces a new protein profile comparison method. It enhances distant homology detection, outperforming existing tools like PSI-BLAST and IMPALA, especially in identifying weak sequence similarities.
Area of Science:
- Bioinformatics
- Computational Biology
- Structural Biology
Background:
- Profile-based methods are crucial for detecting distant protein homologies.
- Existing tools like PSI-BLAST and IMPALA have limitations in sensitivity.
- Identifying weak similarities is challenging but important for understanding protein evolution.
Purpose of the Study:
- To develop a novel and sensitive profile-profile comparison method.
- To improve the detection of weak and distant homologies between protein families.
- To generate alignments that correlate well with structural similarities.
Main Methods:
- Developed a profile-profile comparison tool that accommodates gaps.
- Assigned a statistical similarity score to assess protein profile relationships.
- Optimized the tool to produce alignments in agreement with structural data.
Main Results:
- The new method significantly outperforms PSI-BLAST and IMPALA in detecting distant homologies.
- Alignments generated by the tool show high correlation with secondary and tertiary structure similarities.
- The method effectively identifies similarities in the 'twilight zone' of sequence similarity.
Conclusions:
- The novel profile-profile comparison approach offers superior sensitivity for homology detection.
- This tool aids in discovering weak evolutionary relationships between protein families.
- The method's strong correlation with structural data validates its biological relevance.
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