Changbong Hyeon1, Greg Morrison2,3, David L. Pincus2, D. Thirumalai2,4
1Department of Chemistry, Chung-Ang University, Seoul 156-756, Republic of Korea
2Biophysics Program, Institute for Physical Science and Technology; and
3School of Engineering and Applied Science, Harvard University, Cambridge, MA 02138; and
4Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742
Tóm tắt
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 δ
fS
=
fS
−
fm
and δ
fQ
=
fm
−
fQ
where
fS
(
fQ
) is the stretch (quench) force and
fm
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
fS
to
fQ
). 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 semiflexible (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.
