The ribosome's energy landscape: Recent insights from computation.

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.