Year: 2023
Type: book-chapter
Abstract: We have evidence from a number of cryogenic electron microscopy (cryo-EM) studies that molecules in solution exist in a continuous distribution of conformational states, far larger in number than the discrete ones identified by the standard methods of maximum likelihood classification such as Relion. In collaboration with the group of Abbas Ourmazd at the University of Wisconsin—Milwaukee, the author group has developed a method for the continuous mapping of states from large number of cryo-EM single-particle snapshots over the past seven years. In each case, the free-energy landscapes obtained from the mapping revealed detailed information about functional pathways. It is time to recognize that molecules may as a rule exhibit a large continuous variation in conformational space and that gathering information about this continuum should be the true goal of functionally oriented structure research.
Author: Joachim Frank
Institution: Columbia University
Language: English
Subfield: Structural Biology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4385346003