Allocating dissipation across a molecular machine cycle to maximize flux

Area of Science:

• Biophysics
• Biochemistry
• Molecular Biology

Background:

• Biomolecular machines harness free energy, typically from ATP hydrolysis, to perform directed work.
• Efficient operation and rapid turnover are key evolutionary drivers for molecular machines.
• Understanding energy allocation is crucial for optimizing molecular machine function.

Purpose of the Study:

• To investigate how the free energy budget of molecular machines can be allocated to maximize functional flux (rate of operation).
• To determine the optimal distribution of energy dissipation across different transitions within a molecular machine cycle.
• To reconcile theoretical models with experimental observations of molecular machine behavior.

Main Methods:

• Theoretical modeling of molecular machine dynamics.
• Analysis of free energy dissipation across different states and transitions.
• Comparison of flux-maximizing strategies under constrained and unconstrained state numbers.

Main Results:

• Unconstrained optimization suggests fewer intermediate states enhance flux.
• When the number of states is fixed, flux maximization requires an uneven, not uniform, allocation of energy dissipation.
• This uneven dissipation pattern aligns with models incorporating both irreversible and reversible transitions.

Conclusions:

• Evolutionary pressures favor efficient energy allocation in molecular machines.
• Optimal flux is achieved through a non-uniform distribution of energy dissipation across machine cycle transitions.
• The findings support models where distinct transitions within evolved molecular machines exhibit significantly different energy dissipation characteristics.