SolubiS

SolubiS identifies stabilizing mutations that reduce protein aggregation by combining TANGO aggregation-propensity prediction with FoldX thermodynamic stability assessment.

Key Features:

• Automated Pipeline: Provides an automated pipeline to systematically analyze protein sequences and propose stabilizing mutations by integrating TANGO and FoldX outputs.
• TANGO Algorithm: Assesses intrinsic aggregation propensity and identifies aggregation-prone regions (APRs) within protein sequences.
• FoldX Empirical Force-Field: Evaluates the thermodynamic impact of proposed mutations on the native protein structure to monitor stability changes.
• Prioritization Plot: Generates a plot of intrinsic aggregation propensity scores of APRs corrected by local stability in the folded structure to prioritize mutation targets.

Scientific Applications:

• Protein production and formulation: Reduce aggregation to increase expression and solubility of recombinant proteins, including enzymes and monoclonal antibodies.
• Therapeutic protein engineering: Select mutations that lower aggregation propensity while preserving structural integrity and functional capacity of therapeutic proteins.

Methodology:

Identification of APRs with TANGO; evaluation of mutation effects on thermodynamic stability with FoldX; combination of TANGO and FoldX results to generate a prioritization plot for mutation selection.