Simultaneous determination of protein structure and dynamics
Top Cited Papers
- 13 January 2005
- journal article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 433 (7022), 128-132
- https://doi.org/10.1038/nature03199
Abstract
We present a protocol for the experimental determination of ensembles of protein conformations that represent simultaneously the native structure and its associated dynamics. The procedure combines the strengths of nuclear magnetic resonance spectroscopy--for obtaining experimental information at the atomic level about the structural and dynamical features of proteins--with the ability of molecular dynamics simulations to explore a wide range of protein conformations. We illustrate the method for human ubiquitin in solution and find that there is considerable conformational heterogeneity throughout the protein structure. The interior atoms of the protein are tightly packed in each individual conformation that contributes to the ensemble but their overall behaviour can be described as having a significant degree of liquid-like character. The protocol is completely general and should lead to significant advances in our ability to understand and utilize the structures of native proteins.Keywords
This publication has 46 references indexed in Scilit:
- Heterogeneity and Inaccuracy in Protein Structures Solved by X-Ray CrystallographyStructure, 2004
- Molecular dynamics simulations of biomoleculesNature Structural & Molecular Biology, 2002
- Predicting Changes in the Stability of Proteins and Protein Complexes: A Study of More Than 1000 MutationsJournal of Molecular Biology, 2002
- Calculation of ensembles of structures representing the unfolded state of an SH3 domainJournal of Molecular Biology, 2001
- Forced unfolding of fibronectin type 3 modules: an analysis by biased molecular dynamics simulationsJournal of Molecular Biology, 1999
- Deviations from Standard Atomic Volumes as a Quality Measure for Protein Crystal StructuresJournal of Molecular Biology, 1996
- Structure of ubiquitin refined at 1.8 Å resolutionJournal of Molecular Biology, 1987
- Comparison of simple potential functions for simulating liquid waterThe Journal of Chemical Physics, 1983
- CHARMM: A program for macromolecular energy, minimization, and dynamics calculationsJournal of Computational Chemistry, 1983
- The interpretation of protein structures: Total volume, group volume distributions and packing densityJournal of Molecular Biology, 1974