Harmony

Harmony evaluates the compatibility between an amino acid sequence and its proposed three-dimensional protein structure to validate computational models and experimentally determined structures.

Key Features:

• Sequence-Structure Compatibility Assessment: Assigns residue-specific scores based on amino acid exchange patterns to quantify how well a sequence fits a 3D structure.
• Local Environment Analysis: Considers backbone conformation, solvent accessibility, and hydrogen-bonding patterns when scoring residues.
• Error Localization: Maps residue scores onto the structure to identify regions with potential local errors not indicated by internal parameter strains such as bond lengths and Ramachandran angles.
• Homologous Sequence Alignment Integration: Incorporates alignments of homologous sequences, when provided, into the compatibility assessment.

Scientific Applications:

• Model and Experimental Structure Validation: Validates and assesses the fidelity of computationally modeled and experimentally determined protein structures.
• Error Detection from Inverse Folding and Low-Resolution Data: Detects misfolding or mistracing errors that can arise from inverse folding procedures and low-resolution structure determination.
• Protein-structure Database Curation: Identifies problematic regions to improve the reliability of protein structure databases.
• Structure-guided Research and Drug Design: Provides compatibility metrics that inform structure-based analyses in molecular biology and drug design.

Methodology:

Computes residue-level scores from amino acid exchange patterns and local environmental features (backbone conformation, solvent accessibility, hydrogen bonding), optionally using homologous-sequence alignments, and maps these scores onto the 3D structure to reveal local discrepancies beyond stereochemical checks such as bond lengths and Ramachandran angles.