Advanced

Biomolecular cryocrystallography: Structural changes during flash-cooling

Halle, Bertil LU (2004) In Proceedings of the National Academy of Sciences 101(14). p.4793-4798
Abstract
To minimize radiation damage, crystal structures of biological macromolecules are usually determined after rapid cooling to cryogenic temperatures, some 150-200 K below the normal physiological range, The biological relevance of such structures relies on the assumption that flash-cooling is sufficiently fast to kinetically trap the macromolecule and associated solvent in a room-temperature equilibrium state. To test this assumption, we use a two-state model to calculate the structural changes expected during rapid cooling of a typical protein crystal. The analysis indicates that many degrees of freedom in a flash-cooled protein crystal are quenched at temperatures near 200 K, where local conformational and association equilibria may be... (More)
To minimize radiation damage, crystal structures of biological macromolecules are usually determined after rapid cooling to cryogenic temperatures, some 150-200 K below the normal physiological range, The biological relevance of such structures relies on the assumption that flash-cooling is sufficiently fast to kinetically trap the macromolecule and associated solvent in a room-temperature equilibrium state. To test this assumption, we use a two-state model to calculate the structural changes expected during rapid cooling of a typical protein crystal. The analysis indicates that many degrees of freedom in a flash-cooled protein crystal are quenched at temperatures near 200 K, where local conformational and association equilibria may be strongly shifted toward low-enthalpy states. Such cryoartifacts should be most important for strongly solvent-coupled processes, such as hydration of nonpolar cavities and surface regions, conformational switching of solvent-exposed side chains, and weak ligand binding. The dynamic quenching that emerges from the model considered here can also rationalize the glass transition associated with the atomic fluctuations in the protein. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Proceedings of the National Academy of Sciences
volume
101
issue
14
pages
4793 - 4798
publisher
National Acad Sciences
external identifiers
  • wos:000220761200015
  • pmid:15051877
  • scopus:1842687872
ISSN
1091-6490
DOI
10.1073/pnas.0308315101
language
English
LU publication?
yes
id
eda59093-4c0e-4cb8-9739-203b97bd1097 (old id 141095)
date added to LUP
2007-06-29 10:45:13
date last changed
2017-11-19 03:31:24
@article{eda59093-4c0e-4cb8-9739-203b97bd1097,
  abstract     = {To minimize radiation damage, crystal structures of biological macromolecules are usually determined after rapid cooling to cryogenic temperatures, some 150-200 K below the normal physiological range, The biological relevance of such structures relies on the assumption that flash-cooling is sufficiently fast to kinetically trap the macromolecule and associated solvent in a room-temperature equilibrium state. To test this assumption, we use a two-state model to calculate the structural changes expected during rapid cooling of a typical protein crystal. The analysis indicates that many degrees of freedom in a flash-cooled protein crystal are quenched at temperatures near 200 K, where local conformational and association equilibria may be strongly shifted toward low-enthalpy states. Such cryoartifacts should be most important for strongly solvent-coupled processes, such as hydration of nonpolar cavities and surface regions, conformational switching of solvent-exposed side chains, and weak ligand binding. The dynamic quenching that emerges from the model considered here can also rationalize the glass transition associated with the atomic fluctuations in the protein.},
  author       = {Halle, Bertil},
  issn         = {1091-6490},
  language     = {eng},
  number       = {14},
  pages        = {4793--4798},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {Biomolecular cryocrystallography: Structural changes during flash-cooling},
  url          = {http://dx.doi.org/10.1073/pnas.0308315101},
  volume       = {101},
  year         = {2004},
}