HCA (hydrophobic cluster analysis)

HCA (hydrophobic cluster analysis) analyzes protein sequences by mapping hydrophobic clusters on a bidimensional HCA plot to identify globular versus non-globular regions and to infer secondary-structure elements and functional signals in low-sequence-identity families.

Key Features:

• Bidimensional HCA plot: Uses a two-dimensional representation associated with an alpha helicoidal pitch of 3.6 residues per turn and a connectivity distance of 4.
• Cluster–structure correspondence: Optimized configuration provides strong correspondence between hydrophobic clusters and regular secondary structures.
• Globular region detection: Enables distinction between globular and non-globular sequence regions by inspection of cluster patterns.
• Secondary-structure identification: Permits identification of specific secondary-structure elements within detected globular regions.
• High sensitivity: Detects structural and functional signals in families with minimal or undetectable one-dimensional sequence similarity.
• Protein stability and folding insights: Provides information relevant to protein stability and folding based on hydrophobic cluster organization.
• Methodological enhancements: Incorporates refinements since earlier reviews that expand applicability and address additional aspects of protein analysis.

Scientific Applications:

• Protein sequence analysis: Analysis of protein sequences, especially within families exhibiting low sequence identity.
• Secondary-structure prediction: Inference of regular secondary-structure elements from hydrophobic cluster patterns.
• Domain and globularity delineation: Delimitation of globular versus non-globular regions in protein sequences.
• Functional annotation: Prediction of gene or protein functions when conventional sequence-similarity signals are weak or absent.
• Genomic data interpretation: Exploration and interpretation of large datasets produced by genome sequencing projects.
• Structural biophysics studies: Investigation of aspects of protein stability and folding based on cluster organization.

Methodology:

Construct a bidimensional HCA plot using an alpha helicoidal pitch of 3.6 residues per turn (connectivity distance 4) and map hydrophobic clusters on the plot to infer correspondence with regular secondary structures and to distinguish globular from non-globular regions.