  The atomistic characterization of the transition state is a fundamental step
to improve the understanding of the folding mechanism and the function of
proteins. From a computational point of view, the identification of the
conformations that build out the transition state is particularly cumbersome,
mainly because of the large computational cost of generating a
statistically-sound set of folding trajectories. Here we show that a biasing
algorithm, based on the physics of the ratchet-and-pawl, can be used to
identify efficiently the transition state. The basic idea is that the
algorithmic ratchet exerts a force on the protein when it is climbing the
free-energy barrier, while it is inactive when it is descending. The transition
state can be identified as the point of the trajectory where the ratchet
changes regime. Besides discussing this strategy in general terms, we test it
within a protein model whose transition state can be studied independently by
plain molecular dynamics simulations. Finally, we show its power in
explicit-solvent simulations, obtaining and characterizing a set of
transition--state conformations for ACBP and CI2.
