Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 47, Pages 18943-18948Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1108363108
Keywords
free-energy landscape; modeling transient configurations; molecular machine; tRNA hybrid; translation
Categories
Funding
- Los Alamos National Laboratory (LANL) Laboratory Directed Research and Development
- National Institutes of Health [R01-GM072686]
- National Science Foundation (NSF) [PHY-0822283, NSF-MCB-1051438, NSF-MCB-0744732]
- Deutsche Forschungsgemeinschaft DFG [SFB 740 TP A3, TP Z1, SP 1130/2-1]
- LANL
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [1214457] Funding Source: National Science Foundation
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The dynamic nature of biomolecules leads to significant challenges when characterizing the structural properties associated with function. While X-ray crystallography and imaging techniques (such as cryo-electron microscopy) can reveal the structural details of stable molecular complexes, strategies must be developed to characterize configurations that exhibit only marginal stability (such as intermediates) or configurations that do not correspond to minima on the energy landscape (such as transition-state ensembles). Here, we present a methodology (MDfit) that utilizes molecular dynamics simulations to generate configurations of excited states that are consistent with available biophysical and biochemical measurements. To demonstrate the approach, we present a sequence of configurations that are suggested to be associated with transfer RNA (tRNA) movement through the ribosome (translocation). The models were constructed by combining information from X-ray crystallography, cryo-electron microscopy, and biochemical data. These models provide a structural framework for translocation that may be further investigated experimentally and theoretically to determine the precise energetic character of each configuration and the transition dynamics between them.
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