ConSeq

ConSeq identifies residues within protein sequences that are likely to be functionally or structurally important by integrating evolutionary conservation and solvent accessibility information.

Key Features:

• Multiple Sequence Alignment: Generates a multiple sequence alignment of the target protein with its homologs to inform conservation analysis.
• Evolutionary Rate Estimation: Computes evolutionary rates at each amino acid position from the alignment.
• Relative Solvent Accessibility Estimation: Estimates relative solvent accessibility for each residue.
• Integration of Signals: Integrates evolutionary conservation and solvent exposure to predict residues of functional or structural importance.
• Residue Classification: Distinguishes conserved solvent-accessible residues (indicative of ligand-binding or protein–protein interaction sites) from conserved buried residues (indicative of structural core roles).

Scientific Applications:

• Function Prediction: Identifies conserved, solvent-accessible residues to predict potential ligand-binding sites and protein–protein interaction interfaces.
• Structural Analysis: Identifies conserved core residues to elucidate regions critical for maintaining protein three-dimensional structure.
• Comparative Studies: Enables comparison of its predictions with other prediction methods for validation and refinement.
• Exploration of Unknown Proteins: Applied to predict important residues in proteins of unknown function, including an application to 111 proteins of unknown function.
• Validation and Benchmarking: Methodology and performance were validated using a set of five well-documented proteins with comparisons to other methods.

Methodology:

Generate a multiple sequence alignment of the target with homologs, estimate evolutionary rates and relative solvent accessibility at each amino acid position, and integrate conservation and solvent exposure to predict functionally and structurally important residues.