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The ribosome’s energy landscape: Recent insights from computation

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Abstract

The ever-increasing capacity of computing resources has extended ribosome calculations from the study of small-scale fluctuations to large-scale barrier-crossing processes. As the field of computational/theoretical biophysics shifts focus to large-scale conformational transitions, there is a growing need for a systematic framework to interpret and analyze ribosome dynamics. To this end, energy landscape principles, largely developed for the study of biomolecular folding, have proven to be invaluable. These tools not only provide a foundation for describing simulations but can be used to reconcile experimental results, as well. In this review, I will discuss recent efforts to employ computational methods to reveal the characteristics of the ribosome’s landscape and how these studies can help guide a new generation of experiments that more closely probe the underlying energetics. As a result of these investigations, general principles about ribosome function are beginning to emerge, including that: (1) small-scale fluctuations are the result of structure, rather than detailed energetics, (2) molecular flexibility leads to entropically favored rearrangements, and (3) tRNA dynamics may be accurately described as diffusive movement across an energy landscape.

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Funding

This work was supported by an NSF CAREER Award (Grant MCB-1350312). This work was supported in part by the National Science Foundation through XSEDE resources provided by TACC under Grant No. TG-MCB110021. We also acknowledge generous support provided by the Northeastern University Discovery Cluster.

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Paul Whitford declares that he has no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by the author.

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Correspondence to Paul Charles Whitford.

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Whitford, P.C. The ribosome’s energy landscape: Recent insights from computation. Biophys Rev 7, 301–310 (2015). https://doi.org/10.1007/s12551-014-0155-1

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