Temperature-Dependent Estimation of Gibbs Energies Using an Updated Group-Contribution Method

Area of Science:

• Biochemistry
• Thermodynamics
• Metabolic Engineering

Background:

• Reaction-equilibrium constants are crucial for determining metabolite concentrations and driving flux in metabolic pathways.
• Group-contribution methods provide a scalable approach to estimate these constants across metabolic networks.
• Existing methods lack comprehensive thermodynamic data and temperature-dependent calculations.

Purpose of the Study:

• To present an updated group-contribution method for estimating reaction-equilibrium constants.
• To incorporate additional curated thermodynamic data and enable temperature-dependent calculations.
• To improve the accuracy and applicability of thermodynamic predictions in metabolic studies.

Main Methods:

• Collected and curated extensive aqueous thermodynamic data, including equilibrium constants and formation properties.
• Developed a model to calculate standard entropy change of formation (Δ_fS^∘) based on molecular properties.
• Estimated metal-ion (magnesium) binding constants using linear regression validated against experimental data.

Main Results:

• The updated method demonstrates improved performance in estimating equilibrium constants for new reactions compared to state-of-the-art methods.
• Achieved a median absolute error of 0.013 kJ/K/mol for Δ_fS^∘ estimation.
• Successfully estimated magnesium binding constants for 618 compounds.

Conclusions:

• The enhanced group-contribution method provides more accurate thermodynamic calculations under varying temperatures and metal-ion concentrations.
• This work fills critical gaps in thermodynamic data availability for metabolic studies.
• The improved capabilities empower research into the thermodynamic driving forces of metabolic functions in diverse organisms.