ICARUS

ICARUS performs flexible protein structure alignment by identifying conserved Protein Units (PUs) and hinge positions to compare protein chains across conformational and evolutionary variation.

Key Features:

• Protein Peeling algorithm: Implements the Protein Peeling algorithm (Gelly et al., 2006a; Gelly et al., 2006b; Gelly et al., 2011; Postic et al., 2017; Cretin et al., 2022) for structural segmentation.
• Protein Units (PUs): Identifies intermediate-sized, evolutionarily conserved structural descriptors (PUs) situated between secondary structures and domains.
• Rigid-unit representation: Treats PUs as rigid entities to anchor alignments while explicitly delineating hinge positions for flexibility.
• Flexible alignment handling: Accommodates conformational variability including insertions, circular permutations, and repetitions during alignment.
• Conformational-state comparison: Enables comparison of protein chains in different conformational states, including changes induced by ligands or post-translational modifications.
• Evolutionary sensitivity: Enhances detection of conserved regions across distant evolutionary relationships.
• Benchmarking: Demonstrated superior performance relative to reference methods on challenging structural alignment datasets.

Scientific Applications:

• Flexible structural alignment: Aligns proteins while accounting for domain movements and hinge-borne flexibility.
• Comparative structural analysis: Identifies conserved PUs and structural correspondences across homologs with conformational differences.
• Evolutionary studies: Maps conserved intermediate structural units to investigate evolutionary relationships and rearrangements.
• Analysis of conformational changes: Assesses structural effects of ligand binding and post-translational modifications.
• Handling complex topologies: Compares proteins that exhibit insertions, circular permutations, or internal repeats.

Methodology:

Identification of Protein Units using the Protein Peeling algorithm to define rigid PUs and hinge positions for flexible structural alignment.