Explicit formulation of titration models for isothermal titration calorimetry

Area of Science:

• Biochemistry
• Physical Chemistry
• Biophysics

Background:

• Isothermal titration calorimetry (ITC) is a sensitive technique for studying biomolecular interactions in solution.
• Current data analysis relies on indirect numerical methods based on integrated variables.
• These indirect methods can limit the depth of thermodynamic analysis.

Purpose of the Study:

• To present a direct numerical approach for formulating and fitting ITC data.
• To model ITC data using initial value problems solved as ordinary differential equations (ODEs).
• To enhance the analysis of thermodynamic parameters for biomolecular interactions.

Main Methods:

• Formulating ITC models as first-order ordinary differential equations (ODEs).
• Using total titrant concentration as the independent variable.
• Solving ODEs as numerical initial value problems for data fitting and simulation.

Main Results:

• The direct ODE approach was successfully applied to ligand-receptor binding and homotropic dissociation models.
• Qualitative analysis of ODEs provided insights into model behavior not achievable with indirect methods.
• Numerical ODEs demonstrated compatibility with regression analysis for ITC data.

Conclusions:

• The direct ODE method offers a more insightful and flexible approach to ITC data analysis.
• This approach facilitates the development of custom ITC models for diverse experimental systems.
• Implementation on standard computing platforms makes this method accessible to researchers.