Chemistry Reference
In-Depth Information
Figure 13.8 Folding time dependence on chain length. A plot of
the folding time,
t
F
, versus the number of amino acids, N, is
shown here. The solid blue line shows the fit to a barrier-activated
process,
Aexp(0.6N
g
), where A
t
F
¼
¼
0.002 s and
g ¼
0.57 [98].
could then be found, as well as its dependence on the number of amino acids. These
experiments revealed that the exponential scaling law for a barrier-activated process,
where
t
f
¼ t
corr
exp(0.6 N
0.57
/k
B
T),
fits the data very well (Figure 13.8) with
2
ms [98]. It is interesting to note the similarity between the formof the experimentally-
derived scaling law for the activated transition and that from the mutipathway
mechanism model (Equation 13.6). These force-extension refolding experiments,
performed at zero force, are therefore in good agreement with current physical
models.
The trend observed in the force extension experiments supports the view of
protein folding in a complex energy landscape, in which the conformational degrees
of freedom are affected by the size of the protein chain. This result has been
con
rmed by numerous numerical simulations on model proteins of varying
lengths. However, previous ensemble folding experiments from bulk studies have
argued that the folding times are solely determined by the native state topology,
exhibiting little or no correlation with chain length [99]. These experiments were
performed on a wide variety of proteins, where the distinct amino acid sequence and
topology of the native structure may have played a dominant role in the folding
timescales.
These results emphasize the importance of single-molecule experiments in
improving our understanding of the physical picture underlying the folding
process. Physical models provide clear theoretical predictions for the folding me-
chanisms of proteins. There is an urgent requirement for the development of
physical models which incorporate force as a perturbation along a well-de
t
corr
¼
ned
reaction coordinate. It is also evident that the folding process is not simply driven by
entropy but rather is a result of a subtle interplay between the enthalpic contributions
of residues in the protein chain and the entropy of the surrounding solvent
environment [92, 100
-
103]. By studying how the folding trajectories respond to a
variety of physical
-
chemical conditions and protein engineering it will be possible to
uncover the physical phenomena underlying each stage in the protein folding
trajectories.
