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Title: Trajectories of the ribosome as a Brownian nanomachine

In a Brownian machine, there is a tiny device buffeted by the random motions of molecules in the environment, is capable of exploiting these thermal motions for many of the conformational changes in its work cycle. Such machines are now thought to be ubiquitous, with the ribosome, a molecular machine responsible for protein synthesis, increasingly regarded as prototypical. We present a new analytical approach capable of determining the free-energy landscape and the continuous trajectories of molecular machines from a large number of snapshots obtained by cryogenic electron microscopy. We demonstrate this approach in the context of experimental cryogenic electron microscope images of a large ensemble of nontranslating ribosomes purified from yeast cells. The free-energy landscape is seen to contain a closed path of low energy, along which the ribosome exhibits conformational changes known to be associated with the elongation cycle. This approach allows model-free quantitative analysis of the degrees of freedom and the energy landscape underlying continuous conformational changes in nanomachines, including those important for biological function.
 [1] ;  [1] ;  [2] ;  [1] ;  [2] ;  [1] ;  [2] ;  [3] ;  [2] ;  [4] ;  [4] ;  [4] ;  [5] ;  [1]
  1. Univ. of Wisconsin, Madison, WI (United States). Dept. of Physics
  2. Columbia Univ., New York, NY (United States). Dept. of Biochemistry and Molecular Biophysics
  3. Columbia Univ., New York, NY (United States). Howard Hughes Medical Inst.
  4. Univ. of Maryland Baltimore County (UMBC), Baltimore, MD (United States). Dept. of Cell Biology and Molecular Genetics
  5. Columbia Univ., New York, NY (United States). Dept. of Biochemistry and Molecular Biophysics and Howard Hughes Medical Inst.
Publication Date:
Grant/Contract Number:
SC0002164; R01 GM29169; GM55440; 1157906; FG02-09ER16114
Published Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 111; Journal Issue: 49; Journal ID: ISSN 0027-8424
National Academy of Sciences, Washington, DC (United States)
Research Org:
Univ. of Wisconsin, Milwaukee, WI (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); National Institutes of Health (NIH); National Science Foundation (NSF)
Country of Publication:
United States
60 APPLIED LIFE SCIENCES; cryo-electron microscopy; elongation cycle; manifold embedding; nanomachines; translation
OSTI Identifier:
Alternate Identifier(s):
OSTI ID: 1356190