  Experimental observations suggest that proteins follow different pathways
under different environmental conditions. We perform molecular dynamics
simulations of a model of the SH3 domain over a broad range of temperatures,
and identify distinct pathways in the folding transition. We determine the
kinetic partition temperature --the temperature for which the SH3 domain
undergoes a rapid folding transition with minimal kinetic barriers-- and
observe that below this temperature the model protein may undergo a folding
transition via multiple folding pathways. The folding kinetics is characterized
by slow and fast pathways and the presence of only one or two intermediates.
Our findings suggest the hypothesis that the SH3 domain, a protein for which
only two-state folding kinetics was observed in previous experiments, may
exhibit intermediates states under extreme experimental conditions, such as
very low temperatures. A very recent report (Viguera et al., Proc. Natl. Acad.
Sci. USA, 100:5730--5735, 2003) of an intermediate in the folding transition of
the Bergerac mutant of the alpha-spectrin SH3 domain protein supports this
hypothesis.
