Protein high-force pulling simulations yield low-force results

All-atom explicit-solvent molecular dynamics simulations are used to pull with extremely large constant force (750-3000 pN) on three small proteins. The introduction of a nondimensional timescale permits direct comparison of unfolding across all forces. A crossover force of approximately 1100 pN div...

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Bibliographic Details
Published in:PloS one 2012-04, Vol.7 (4), p.e34781-e34781
Main Authors: Lichter, Seth, Rafferty, Benjamin, Flohr, Zachary, Martini, Ashlie
Format: Article
Language:English
Subjects:
Biology
Comparative analysis
Computer simulation
E coli
Engineering schools
Experiments
Hydrodynamics
Molecular dynamics
Molecular Dynamics Simulation
NMR
Nuclear magnetic resonance
Numerical analysis
Numerical simulations
Physics
Protein Conformation
Protein folding
Protein Unfolding
Proteins
Proteins - chemistry
Scaling
Spectrum analysis
Studies
Variation
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Summary:All-atom explicit-solvent molecular dynamics simulations are used to pull with extremely large constant force (750-3000 pN) on three small proteins. The introduction of a nondimensional timescale permits direct comparison of unfolding across all forces. A crossover force of approximately 1100 pN divides unfolding dynamics into two regimes. At higher forces, residues sequentially unfold from the pulling end while maintaining the remainder of the protein force-free. Measurements of hydrodynamic viscous stresses are made easy by the high speeds of unfolding. Using an exact low-Reynolds-number scaling, these measurements can be extrapolated to provide, for the first time, an estimate of the hydrodynamic force on low-force unfolding. Below 1100 pN, but surprisingly still at extremely large applied force, intermediate states and cooperative unfoldings as seen at much lower forces are observed. The force-insensitive persistence of these structures indicates that decomposition into unfolded fragments requires a large fluctuation. This finding suggests how proteins are constructed to resist transient high force. The progression of [Formula: see text] helix and [Formula: see text] sheet unfolding is also found to be insensitive to force. The force-insensitivity of key aspects of unfolding opens the possibility that numerical simulations can be accelerated by high applied force while still maintaining critical features of unfolding.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0034781