Prediction of native-state hydrogen exchange from perfectly funneled energy landscapes

Authors
Craig, Patricio Oliver; Lätzer, Joachim; Weinkam, Patrick; Hoffman, Ryan M. B.; Ferreiro, Diego; Komives, Elizabeth A.; Wolynes, Peter G.
Publication Year
2011
Language
English
Format
article
Status
Published version
Description
Simulations based on perfectly funneled energy landscapes often capture many of the kinetic features of protein folding. We examined whether simulations based on funneled energy functions can also describe fluctuations in native-state protein ensembles. We quantitatively compared the site-specific local stability determined from structure-based folding simulations, with hydrogen exchange protection factors measured experimentally for ubiquitin, chymotrypsin inhibitor 2, and staphylococcal nuclease. Different structural definitions for the open and closed states based on the number of native contacts for each residue, as well as the hydrogen-bonding state, or a combination of both criteria were evaluated. The predicted exchange patterns agree with the experiments under native conditions, indicating that protein topology indeed has a dominant effect on the exchange kinetics. Insights into the simplest mechanistic interpretation of the amide exchange process were thus obtained.
Fil: Craig, Patricio Oliver. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. University of California San Diego. Department of Chemistry and Biochemistry; Estados Unidos
Fil: Lätzer, Joachim. Rutgers University. BioMaPS Institute; Estados Unidos
Fil: Weinkam, Patrick. University of California at San Francisco. Department of Bioengineering and Therapeutic Sciences; Estados Unidos
Fil: Hoffman, Ryan M. B.. University Of California At San Diego; Estados Unidos
Fil: Ferreiro, Diego. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Komives, Elizabeth A.. University Of California At San Diego; Estados Unidos
Fil: Wolynes, Peter G.. University Of California At San Diego; Estados Unidos
Subject
protein folding
hydrogen exchange
energy landscape
coarse grain models
Biofísica
Ciencias Biológicas
CIENCIAS NATURALES Y EXACTAS
Biofísica
Ciencias Biológicas
CIENCIAS NATURALES Y EXACTAS
Access level
Open access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/13824