  Although known that single domain proteins fold and unfold by parallel
pathways, demonstration of this expectation has been difficult to establish in
experiments. Unfolding rate, $k_\mathrm{u}(f)$, as a function of force $f$,
obtained in single molecule pulling experiments on src SH3 domain, exhibits
upward curvature on a $\log k_\mathrm{u}(f)$ plot. Similar observations were
reported for other proteins for the unfolding rate $k_\mathrm{u}([C])$. These
findings imply unfolding in these single domain proteins involves a switch in
the pathway as $f$ or $[C]$ is increased from a low to a high value. We provide
a unified theory demonstrating that if $\log k_\mathrm{u}$ as a function of a
perturbation ($f$ or $[C]$) exhibits upward curvature then the underlying
energy landscape must be strongly multidimensional. Using molecular simulations
we provide a structural basis for the switch in the pathways and dramatic
shifts in the transition state ensemble (TSE) in src SH3 domain as $f$ is
increased. We show that a single point mutation shifts the upward curvature in
$\log k_\mathrm{u}(f)$ to a lower force, thus establishing the malleability of
the underlying folding landscape. Our theory, applicable to any perturbation
that affects the free energy of the protein linearly, readily explains movement
in the TSE in a $\beta$-sandwich (I27) protein and single chain monellin as the
denaturant concentration is varied. We predict that in the force range
accessible in laser optical tweezer experiments there should be a switch in the
unfolding pathways in I27 or its mutants.
