Thermodynamic Activation Parameters for Chemical Reactions in Enzymes and Solution from Computer Simulations at a...

Area of Science:

• Biochemistry
• Computational Chemistry
• Enzyme Kinetics

Background:

• Enzyme adaptation to temperature regimes is linked to distinct activation enthalpies and entropies.
• Predicting enzyme psychrophilicity or mesophily is possible using activation parameters.
• Standard computational methods involve multi-temperature simulations to construct Arrhenius plots.

Purpose of the Study:

• To investigate an alternative computational approach for analyzing enzyme temperature dependence.
• To assess the reliability of a single-temperature free energy simulation method for calculating enthalpy and entropy.
• To explore new avenues for analyzing nonlinear Arrhenius behavior and enthalpy decomposition.

Main Methods:

• Calculated reaction free energy profiles at multiple temperatures to construct computational Arrhenius plots.
• Re-examined the performance of an averaging method for enthalpy calculation using single-temperature free energy simulations.
• Applied the averaging method to two solution reactions and one enzyme reaction.

Main Results:

• Multi-temperature simulations, while informative, are computationally demanding and limit enthalpy decomposition.
• The averaging method, previously deemed unreliable, demonstrated surprising accuracy with sufficient data.
• Enthalpy profiles obtained via averaging are decomposable into different energy terms.

Conclusions:

• The averaging method provides a computationally efficient and reliable alternative for studying enzyme temperature dependence.
• This approach facilitates a deeper understanding of nonlinear Arrhenius behavior by enabling enthalpy decomposition.
• The findings open new possibilities for analyzing enzyme energetics and adaptation mechanisms.