SETTER

SETTER compares RNA tertiary and quaternary structures by decomposing them into generalized secondary structure units (GSSUs) to enable efficient pairwise similarity assessment, and MultiSETTER extends this approach to multiple-structure alignment.

Key Features:

• Pairwise structure comparison (SETTER): Decomposes RNA 3D structures into non-overlapping generalized secondary structure units (GSSUs) for structure-based pairwise comparison.
• Multiple structure alignment (MultiSETTER): Extends GSSU decomposition to align multiple RNA structures using a structure-adapted alignment strategy.
• Integration with ClustalW: Employs a modified version of the ClustalW algorithm adapted for structural data to perform multiple-structure alignments.
• Algorithmic decomposition (GSSUs): Uses GSSUs as the primary structural elements to reduce complexity of comparing large RNA molecules.
• Computational complexity: Reported to scale approximately O(n^2) with the size of GSSUs and O(n) with their number.
• Supported input formats: Operates on structures provided as PDB files or referenced by PDB IDs.
• Outputs and visualization: Generates 3D visualizations, detailed alignment reports, and statistics.
• Validation and benchmarking: Accuracy and classification performance have been evaluated against SCOR annotations and compared with LocARNA and RNADistance.

Scientific Applications:

• Understanding RNA functionality: Enables structural comparisons that support inference of functional roles for regulatory non-coding RNAs.
• Evolutionary analysis: Identifies evolutionarily conserved structural features that may be obscured at the sequence or secondary-structure level.
• Structural classification: Supports classification and benchmarking of RNA tertiary/quaternary structures against reference annotations and alternative alignment methods.

Methodology:

Decomposes RNA structures into GSSUs for comparison and uses a ClustalW-based algorithm modified for structural data to perform multiple-structure alignment, with reported computational scaling of O(n^2) by GSSU size and O(n) by GSSU number.