All-atom simulation of the HET-s prion replication
Fig 1
Schematic representation of the SCPS algorithm.
XI represents the initial protein conformation, XF the final target conformation and T1 …N the trajectories connecting XI to XF. Step 1: an ensemble of trajectories starting from XI and successfully reaching XF is generated by employing the rMD, biasing along the pre-defined CV z(X). Since z(X) decreases when the proximity of X to XF increases, the progression along the path is here defined as −z(X). Step 2: the trajectories successfully reaching the target state are then used to compute the mean path ⟨Cij(t)⟩, depicted in purple (see Methods). The mean path is then used to define two new coordinates: sλ, depicted in blue, which value is 1 in the unstructured state and 0 in the target state, therefore (1 − sλ) is used here to define the progress along the mean path; and wλ, depicted in red, that represents the distance to the mean path. Step 3: a modified version of the rMD is employed to generate a new set of trajectories by introducing two biasing forces, acting along sλ(t), and wλ(t) instead of z(X). The trajectories successfully reaching the target state are then used to compute a new mean path (step 2) to perform a new iteration.