FuzDrop

FuzDrop predicts sequence-dependent propensities for liquid-liquid phase separation (LLPS) and aggregation to identify droplet-promoting regions, aggregation hot-spots, and mutation effects relevant to membraneless organelles.

Key Features:

• Prediction of Liquid-Liquid Phase Separation: Calculates sequence-based probabilities and scores of spontaneous LLPS to identify regions that promote droplet formation.
• Identification of Aggregation Hot-Spots: Estimates propensity to transition into amyloid states and pinpoints aggregation hot-spots that may drive irreversible droplet maturation.
• Mutation Analysis: Identifies mutations predicted to induce amyloid aggregate formation implicated in human diseases.
• Visualization on Protein Structures: Maps droplet-promoting and aggregation-promoting regions onto protein structures generated by AlphaFold for structural interpretation.

Scientific Applications:

• Cellular Organization: Characterizing protein condensation and compartmentalization within membraneless organelles.
• Protein Function in Membraneless Organelles: Linking sequence determinants of LLPS and aggregation to protein function in membraneless organelles.
• Pathological Aggregation and Disease Mechanisms: Investigating the pathological implications of protein aggregation, including amyloid formation and disease-related mutations.
• Therapeutic Target Identification: Aiding identification of sequence regions and mutations as potential targets for therapeutic intervention.

Methodology:

Performs sequence-based computational predictions of LLPS and aggregation propensities and integrates these predictions with AlphaFold structural data for visualization.