Refolding dynamics of stretched biopolymers upon force quench

摘要

Single-molecule force spectroscopy methods can be used to generate folding trajectories of biopolymers from arbitrary regions of the folding landscape. We illustrate the complexity of the folding kinetics and generic aspects of the collapse of RNA and proteins upon force quench by using simulations of an RNA hairpin and theory based on the de Gennes model for homopolymer collapse. The folding time, τ_F. depends asymmetrically on δf_s = f_s - f_m and δf_Q = f_m - f_Q where f_s (f_Q) is the stretch (quench) force and f_m is the transition midforce of the RNA hairpin. In accord with experiments, the relaxation kinetics of the molecular extension, R(t), occurs in three stages: A rapid initial decrease in the extension is followed by a plateau and finally, an abrupt reduction in R(t) occurs as the native state is approached. The duration of the plateau increases as λ = τ_q/τ_F decreases (where τ_Q is the time in which the force is reduced from f_s to f_Q. Variations in the mechanisms of force-quench relaxation as λ is altered are reflected in the experimentally measurable time-dependent entropy, which is computed directly from the folding trajectories. An analytical solution of the de Gennes model under tension reproduces the multistage stage kinetics in R(t). The prediction that the initial stages of collapse should also be a generic feature of polymers is validated by simulation of the kinetics of toroid (globule) formation in semiflex-ible (flexible) homopolymers in poor solvents upon quenching the force from a fully stretched state. Our findings give a unified explanation for multiple disparate experimental observations of protein folding.