Simultaneous determination of protein structure and dynamics
Kresten Lindorff‐Larsena b c, Robert B. Bestb d e, Mark A. DePristof g h, Christopher Martin Dobsond i j k✉, Michele Vendruscolod i j k✉
- aDepartment of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK
- bDepartment of Chemistry, University of Cambridge, Cambridge, UK
- cDepartment of Protein Chemistry, Institute of Molecular Biology, University of Copenhagen, Copenhagen K, Denmark
- dDepartment of Chemistry, University of Cambridge, Cambridge, Lensfield Road, CB2 1EW, UK
- eLaboratory of Chemical Physics, NIDDK, National Institutes of Health, Bethesda, USA
- fDepartment of Biochemistry, University of Cambridge, Cambridge, 80 Tennis Court Road, CB2 1GA, UK
- gDepartment of Biochemistry, University of Cambridge, Cambridge, UK
- hDepartment of Organismic and Evolutionary Biology, Harvard University, Cambridge, USA
- iDepartment of Chemistry
- jUniversity of Cambridge
- kCambridge
- ✉Corresponding author
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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.
TL;DRThe 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. (Semantic Scholar)