Constructing a folding model for protein S6 guided by native fluctuations deduced from NMR structures
Abstract
The diversity in a set of protein nuclear magnetic resonance (NMR) structures provides an estimate of native state fluctuations that can be used to refine and enrich structure-based protein models (SBMs). Dynamics are an essential part of a protein’s functional native state. The dynamics in the native state are controlled by the same funneled energy landscape that guides the entire folding process. SBMs apply the principle of minimal frustration, drawn from energy landscape theory, to construct a funneled folding landscape for a given protein using only information from the native structure. On an energy landscape smoothed by evolution towards minimal frustration, geometrical constraints, imposed by the native structure, control the folding mechanism and shape the native dynamics revealed by the model. Native-state fluctuations can alternatively be estimated directly from the diversity in the set of NMR structures for a protein. Based on this information, we identify a highly flexible loop in the ribosomal protein S6 and modify the contact map in a SBM to accommodate the inferred dynamics. By taking into account the probable native state dynamics, the experimental transition state is recovered in the model, and the correct order of folding events is restored. Our study highlights how themore »
- Authors:
-
- Steinbuch Centre for Computing, Karlsruhe Institute of Technology, Karlsruhe (Germany)
- Publication Date:
- OSTI Identifier:
- 22493380
- Resource Type:
- Journal Article
- Journal Name:
- Journal of Chemical Physics
- Additional Journal Information:
- Journal Volume: 143; Journal Issue: 24; Other Information: (c) 2015 AIP Publishing LLC; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0021-9606
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL CHEMISTRY; CONTROL; FLUCTUATIONS; FOLDING MODEL; NUCLEAR MAGNETIC RESONANCE; PROTEINS; RIBOSOMES
Citation Formats
Lammert, Heiko, Noel, Jeffrey K., Haglund, Ellinor, Onuchic, José N., E-mail: jonuchic@rice.edu, and Schug, Alexander. Constructing a folding model for protein S6 guided by native fluctuations deduced from NMR structures. United States: N. p., 2015.
Web. doi:10.1063/1.4936881.
Lammert, Heiko, Noel, Jeffrey K., Haglund, Ellinor, Onuchic, José N., E-mail: jonuchic@rice.edu, & Schug, Alexander. Constructing a folding model for protein S6 guided by native fluctuations deduced from NMR structures. United States. https://doi.org/10.1063/1.4936881
Lammert, Heiko, Noel, Jeffrey K., Haglund, Ellinor, Onuchic, José N., E-mail: jonuchic@rice.edu, and Schug, Alexander. 2015.
"Constructing a folding model for protein S6 guided by native fluctuations deduced from NMR structures". United States. https://doi.org/10.1063/1.4936881.
@article{osti_22493380,
title = {Constructing a folding model for protein S6 guided by native fluctuations deduced from NMR structures},
author = {Lammert, Heiko and Noel, Jeffrey K. and Haglund, Ellinor and Onuchic, José N., E-mail: jonuchic@rice.edu and Schug, Alexander},
abstractNote = {The diversity in a set of protein nuclear magnetic resonance (NMR) structures provides an estimate of native state fluctuations that can be used to refine and enrich structure-based protein models (SBMs). Dynamics are an essential part of a protein’s functional native state. The dynamics in the native state are controlled by the same funneled energy landscape that guides the entire folding process. SBMs apply the principle of minimal frustration, drawn from energy landscape theory, to construct a funneled folding landscape for a given protein using only information from the native structure. On an energy landscape smoothed by evolution towards minimal frustration, geometrical constraints, imposed by the native structure, control the folding mechanism and shape the native dynamics revealed by the model. Native-state fluctuations can alternatively be estimated directly from the diversity in the set of NMR structures for a protein. Based on this information, we identify a highly flexible loop in the ribosomal protein S6 and modify the contact map in a SBM to accommodate the inferred dynamics. By taking into account the probable native state dynamics, the experimental transition state is recovered in the model, and the correct order of folding events is restored. Our study highlights how the shared energy landscape connects folding and function by showing that a better description of the native basin improves the prediction of the folding mechanism.},
doi = {10.1063/1.4936881},
url = {https://www.osti.gov/biblio/22493380},
journal = {Journal of Chemical Physics},
issn = {0021-9606},
number = 24,
volume = 143,
place = {United States},
year = {Mon Dec 28 00:00:00 EST 2015},
month = {Mon Dec 28 00:00:00 EST 2015}
}