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Contributed by Ken A. Dill, January 28, 2019 (sent for review July 16, 2018; reviewed by Jonathon Howard and Daniel M. Zuckerman)
Significance
Molecular machines are cellular proteins that transduce energy. They can convert energy to motion, recharge ATP stores by harnessing ion flows, and pump ions energetically uphill. Molecular machines are able to be both fast and efficient at the same time. How do they achieve high speeds at high efficiency? Here we explore mechanisms of evolution or synthetic design that can optimize these properties, such as a conformationally driven mechanical step, which varies the conformational free-energy landscape to mitigate large kinetic barriers, and mechanical substeps, which split one large kinetic barrier into multiple smaller ones.
Abstract
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.
Footnotes
- ↵1To whom correspondence should be addressed. Email: dill{at}laufercenter.org.
Author contributions: J.A.W. and K.A.D. designed research; J.A.W. performed research; J.A.W. analyzed data; and J.A.W. and K.A.D. wrote the paper.
Reviewers: J.H., Yale University; and D.M.Z., Oregon Health & Science University.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1812149116/-/DCSupplemental.
Published under the PNAS license.
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Mechanisms for achieving high speed and efficiency in biomolecular machines
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