catKLS

catKLS models proteolytic network dynamics focusing on protease-as-substrate interactions among cysteine cathepsins to predict substrate degradation and changes in protease concentrations.

Key Features:

• Protease-As-Substrate Dynamics: Accounts for protease-on-protease inactivating hydrolysis that alters predicted protease concentrations.
• Cysteine Cathepsins Focus: Specifically models cysteine cathepsins and "cathepsin cannibalism," where one cathepsin hydrolyzes another in the presence of substrate.
• Computational Modeling: Utilizes computational models to represent cooperative and competitive degradation by multiple proteases with simultaneous substrate cleavage.
• Parameter Optimization: Performs parameter optimization that can reveal additional reaction nodes such as distraction reactions in which inactivated proteases act as competitive inhibitors.
• Incorporation of Complex Reactions: Includes explicit terms for autodigestion, inactivation, cannibalism, and distraction within its kinetic predictive framework.

Scientific Applications:

• Proteolytic Network Analysis: Predicts substrate degradation rates and protease concentration dynamics in multiprotease systems, particularly for cysteine cathepsins.
• Drug Development and Dosing Strategies: Informs pharmaceutical dosing and therapeutic intervention planning by accounting for enzyme loss due to proteolytic degradation.
• Hypothesis Testing of Perturbations: Enables simulation of perturbations involving multiple cathepsins, substrates, and inhibitors to predict shifts in network reactions and system dynamics.

Methodology:

Uses computational models with parameter optimization to fit kinetic models and incorporates terms for autodigestion, inactivation, cannibalism, distraction, and simultaneous substrate cleavage to simulate cooperative and competitive protease degradation.