Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 116, Issue 13, Pages 5902-5907Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1812149116
Keywords
molecular machines; evolution; nonequilibrium steady state; kinetic optimization; free-energy landscape
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Funding
- Laufer Center for Physical and Quantitative Biology
- NIH [GM06359217]
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How does a biomolecular machine achieve high speed at high efficiency? We explore optimization principles using a simple two-state dynamical model. With this model, we establish physical principles-such as the optimal way to distribute free-energy changes and barriers across the machine cycle-and connect them to biological mechanisms. We find that a machine can achieve high speed without sacrificing efficiency by varying its conformational free energy to directly link the downhill, chemical energy to the uphill, mechanical work and by splitting a large work step into more numerous, smaller substeps. Experimental evidence suggests that these mechanisms are commonly used by biomolecular machines. This model is useful for exploring questions of evolution and optimization in molecular machines.
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