We
use Langevin dynamics simulations to model, at an atomistic
resolution, how various natively knotted proteins are unfolded in
repeated allosteric translocating cycles of the ClpY ATPase. We consider
proteins representative of different topologies, from the simplest
knot (trefoil 31), to the three-twist 52 knot,
to the most complex stevedore, 61, knot. We harness the
atomistic detail of the simulations to address aspects that have so
far remained largely unexplored, such as sequence-dependent effects
on the ruggedness of the landscape traversed during knot sliding.
Our simulations reveal the combined effect on translocation of the
knotted protein structure, i.e., backbone topology and geometry, and
primary sequence, i.e., side chain size and interactions, and show
that the latter can dominate translocation hindrance. In addition,
we observe that due to the interplay between the knotted topology
and intramolecular contacts the transmission of tension along the
polypeptide chain occurs very differently from that of homopolymers.
Finally, by considering native and non-native interactions, we examine
how the disruption or formation of such contacts can affect the translocation
processivity and concomitantly create multiple unfolding pathways
with very different activation barriers.