title: Protein high-force pulling simulations yield low-force results.
abstract: 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.
authors.affiliation: Department of Mechanical Engineering, Northwestern University, Evanston, Illinois, United States of America. s-lichter@northwestern.edu
authors.forename: Seth
authors.initials: S
authors.lastname: Lichter
authors.forename: Benjamin
authors.initials: B
authors.lastname: Rafferty
authors.forename: Zachary
authors.initials: Z
authors.lastname: Flohr
authors.forename: Ashlie
authors.initials: A
authors.lastname: Martini
mesh_terms: D057446:Hydrodynamics; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D058767:Protein Unfolding; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins