title: Capturing transition paths and transition states for conformational rearrangements in the ribosome.
abstract: To reveal the molecular determinants of biological function, one seeks to characterize the interactions that are formed in conformational and chemical transition states. In other words, what interactions govern the molecule's energy landscape? To accomplish this, it is necessary to determine which degrees of freedom can unambiguously identify each transition state. Here, we perform simulations of large-scale aminoacyl-transfer RNA (aa-tRNA) rearrangements during accommodation on the ribosome and project the dynamics along experimentally accessible atomic distances. From this analysis, we obtain evidence for which coordinates capture the correct number of barrier-crossing events and accurately indicate when the aa-tRNA is on a transition path. Although a commonly used coordinate in single-molecule experiments performs poorly, this study implicates alternative coordinates along which rearrangements are accurately described as diffusive movements across a one-dimensional free-energy profile. From this, we provide the theoretical foundation required for single-molecule techniques to uncover the energy landscape governing aa-tRNA selection by the ribosome.
authors.affiliation: Center for Theoretical Biological Physics, Rice University, Houston, Texas.
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Noel
authors.affiliation: Instituto de Biociências, Letras e Ciências Exatas, Universidade Estadual Paulista, São José do Rio Preto, Brazil.
authors.forename: Jorge
authors.initials: J
authors.lastname: Chahine
authors.affiliation: Instituto de Biociências, Letras e Ciências Exatas, Universidade Estadual Paulista, São José do Rio Preto, Brazil.
authors.forename: Vitor B P
authors.initials: VBP
authors.lastname: Leite
authors.affiliation: Department of Physics, Northeastern University, Boston, Massachusetts. Electronic address: p.whitford@neu.edu.
authors.forename: Paul Charles
authors.initials: PC
authors.lastname: Whitford
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D012343:RNA, Transfer / Q000737:chemistry* / Q000378:metabolism; D012270:Ribosomes / Q000737:chemistry* / Q000378:metabolism
chemical_list: D012343:RNA, Transfer