Prelude Fugue

Prelude Fugue predicts local three-dimensional (3D) protein structure from amino acid sequences by identifying seven distinct backbone torsion angle domains and ranking lowest-free-energy conformations to analyze folding and structural stability.

Key Features:

• Torsion Angle Domains Prediction: Predicts local 3D structure in terms of seven distinct backbone torsion angle domains using database-derived potentials.
• Energy-Based Conformation Ranking: Computes and ranks lowest free energy conformations of a protein or protein region by increasing free energy.
• Interresidue Distance Constraints: Incorporates interresidue distance constraints to refine and constrain predicted conformations.
• Early Folding Sequence Identification: Detects sequence regions that form early during protein folding, including sequences that adopt a preferred conformation in solution.
• Structural Weakness Detection: Identifies sequence regions that are not optimal with respect to the tertiary fold, highlighting potential instability or misfolding sites.

Scientific Applications:

• Secondary and Tertiary Structure Prediction: Predicts secondary and tertiary structures of short peptides through torsion angle domain assignment and energy ranking.
• Flickering Early Folding Sequences Analysis: Analyzes sequences that exhibit early or flickering folding behavior to investigate initial folding events.
• Structural Weakness Identification: Pinpoints regions suboptimal for the tertiary structure to inform studies of stability and misfolding.

Methodology:

Uses database-derived potentials to model conformations, computes the free energy landscape to identify and rank lowest-free-energy conformations by increasing energy, and allows incorporation of interresidue distance constraints.