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A Protocol for Computer-Based Protein Structure and Function Prediction
Published on: November 3, 2011
How significant is a protein structure similarity with TM-score = 0.5?
1Department of Medical School, Center for Computational Medicine and Bioinformatics, University of Michigan, 100 Washtenaw Avenue, Ann Arbor, MI 48109, USA.
Bioinformatics (Oxford, England)
|February 19, 2010
Summary
The Template Modeling score (TM-score) has statistical significance, with a TM-score of 0.5 indicating a very low probability of random structural similarity. This score can quantitatively classify protein folds.
Area of Science:
- Structural bioinformatics
- Computational biology
- Biophysics
Background:
- Protein structure similarity is crucial for understanding function and evolution.
- Current metrics like TM-score lack clear statistical significance and fold classification correlation.
- Quantifying the significance of structural similarity is essential for robust analysis.
Purpose of the Study:
- To determine the statistical significance of the Template Modeling score (TM-score).
- To establish the probability of two proteins sharing the same fold based on TM-score.
- To assess TM-score's utility as a quantitative criterion for protein fold classification.
Main Methods:
- Performed all-to-all gapless structural alignment on 6684 non-homologous single-domain proteins from the Protein Data Bank (PDB).
- Analyzed TM-scores using extreme value distribution to derive P-values.
- Examined posterior probabilities of same-fold proteins across SCOP, CATH, and consensus datasets.
Main Results:
- TM-scores follow an extreme value distribution, allowing P-value assignment for statistical significance.
- A TM-score of 0.5 corresponds to a P-value of 5.5 x 10(-7), implying rare occurrence by chance.
- A rapid phase transition in posterior probability around TM-score=0.5 was observed across datasets.
Conclusions:
- TM-score provides a statistically significant measure of protein structural similarity.
- TM-score serves as a quantitative criterion for protein fold classification, with >0.5 suggesting the same fold.
- The findings facilitate more accurate and reliable protein structure comparison and classification.
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