Order independent structural alignment of circularly permuted proteins

Area of Science:

• Proteomics
• Structural Biology
• Bioinformatics

Background:

• Circular permutation in proteins, where N and C termini are joined and cleavage occurs internally, generates novel folds and functions.
• Current methods for detecting circularly permuted proteins are insufficient, often missing true positives or misidentifying random repeats.

Purpose of the Study:

• To develop an efficient and accurate computational method for identifying circularly permuted proteins using structural comparisons.
• To address the challenge of unknown genomic distribution of circularly permuted proteins due to detection limitations.

Main Methods:

• Developed a novel method based on sequence-order independent alignment of protein structures.
• Employed an efficient approximation algorithm derived from solving relaxations of an integer programming formulation.
• Utilized structural comparison as the core principle for detection.

Main Results:

• The developed method rapidly identifies known circularly permuted proteins from literature.
• The new approach outperforms publicly available structural alignment servers in detecting these proteins.
• Demonstrated a significantly better approximation ratio than the theoretical worst-case for the underlying computational problem.

Conclusions:

• The novel method provides a robust solution for detecting circularly permuted proteins.
• This advancement facilitates a more comprehensive understanding of the prevalence and functional significance of circular permutation in proteomes.
• The computational approach offers improved accuracy and efficiency over existing detection strategies.