Interaction Networks in Protein Folding via Atomic-Resolution Experiments and Long-Time-Scale Molecular Dynamics Simulations

The integration of atomic-resolution experimental and computational methods offers the potential for elucidating key aspects of protein folding that are not revealed by either approach alone. Here, we combine equilibrium NMR measurements of thermal unfolding and long molecular dynamics simulations t...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2015-05, Vol.137 (20), p.6506-6516
Main Authors: Sborgi, Lorenzo, Verma, Abhinav, Piana, Stefano, Lindorff-Larsen, Kresten, Cerminara, Michele, Santiveri, Clara M, Shaw, David E, de Alba, Eva, Muñoz, Victor
Format: Article
Language:English
Subjects:
Hydrogen-Ion Concentration
Models, Molecular
Molecular Dynamics Simulation
Nuclear Magnetic Resonance, Biomolecular
Protein Folding
Proteins - chemistry
Proteins - metabolism
Thermodynamics
Time Factors
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Summary:The integration of atomic-resolution experimental and computational methods offers the potential for elucidating key aspects of protein folding that are not revealed by either approach alone. Here, we combine equilibrium NMR measurements of thermal unfolding and long molecular dynamics simulations to investigate the folding of gpW, a protein with two-state-like, fast folding dynamics and cooperative equilibrium unfolding behavior. Experiments and simulations expose a remarkably complex pattern of structural changes that occur at the atomic level and from which the detailed network of residue–residue couplings associated with cooperative folding emerges. Such thermodynamic residue–residue couplings appear to be linked to the order of mechanistically significant events that take place during the folding process. Our results on gpW indicate that the methods employed in this study are likely to prove broadly applicable to the fine analysis of folding mechanisms in fast folding proteins.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.5b02324