# Allocating dissipation across a molecular machine cycle to maximize flux

## TL;DR

This paper explores how molecular machines can optimally allocate free energy dissipation across their cycle to maximize flux, revealing that fewer states and uneven dissipation distribution enhance efficiency.

## Contribution

It demonstrates that optimal dissipation allocation involves fewer states and uneven dissipation, challenging previous assumptions and aligning with experimental observations.

## Key findings

- Fewer states lead to higher flux.
- Uneven dissipation allocation maximizes flux.
- Evolved machines exhibit varied dissipation across transitions.

## Abstract

Biomolecular machines consume free energy to break symmetry and make directed progress. Nonequilibrium ATP concentrations are the typical free energy source, with one cycle of a molecular machine consuming a certain number of ATP, providing a fixed free energy budget. Since evolution is expected to favor rapid-turnover machines that operate efficiently, we investigate how this free energy budget can be allocated to maximize flux. Unconstrained optimization eliminates intermediate metastable states, indicating that flux is enhanced in molecular machines with fewer states. When maintaining a set number of states, we show that---in contrast to previous findings---the flux-maximizing allocation of dissipation is not even. This result is consistent with the coexistence of both `irreversible' and reversible transitions in molecular machine models that successfully describe experimental data, which suggests that in evolved machines different transitions differ significantly in their dissipation.