Rate turnover in mechano-catalytic coupling: A model and its microscopic origin

Area of Science:

• Biophysics
• Chemical Kinetics
• Computational Biology

Background:

• Mechano-chemistry explores how mechanical forces influence chemical reactions.
• Enzyme activity can be modulated by external forces, a phenomenon known as mechano-catalytic coupling.
• Protein disulfide bond reduction rates exhibit complex force-dependent behavior.

Purpose of the Study:

• To develop a theoretical model explaining the biphasic force dependence of enzyme-catalyzed disulfide bond reduction.
• To elucidate the underlying microscopic mechanisms of mechano-catalysis.
• To provide a framework for predicting enzyme response to mechanical forces.

Main Methods:

• Atomistic molecular dynamics simulations were employed to investigate protein dynamics.
• Smoluchowski theory was applied to model reaction-diffusion processes.
• A quasiharmonic analysis was used to derive model parameters from simulations.
• A reaction-diffusion equation was solved for a force-dependent effective potential.

Main Results:

• The proposed model successfully reproduces experimentally observed bond cleavage rates across a range of forces.
• The model captures the unexpected biphasic force dependence reported in experiments.
• Atomistic simulations provide insights into the microscopic degrees of freedom governing mechano-catalysis.

Conclusions:

• The developed model offers a robust explanation for mechano-catalytic coupling in enzyme-catalyzed reactions.
• Understanding force-dependent enzyme activity is crucial for fields ranging from protein engineering to molecular motors.
• This work bridges atomistic detail with macroscopic reaction kinetics for mechano-enzymatic processes.