Figure 5.

Workflow of a Supervised Molecular Dynamics (SuMD) simulation. The ligand is dynamically docked within a user-defined binding site through a series of short, unbiased molecular dynamics simulations. At the end of each step, the distance of mass between the ligand and the receptor binding site is computed for each trajectory frame and is fed to a tabu-like algorithm. If the slope of the straight line that interpolates the data is negative, indicating the ligand is approaching the binding site, the step is retained, and the simulation continues with the next “SuMD-step”. If not, the step is discarded and repeated, randomly reassigning particles’ velocities through the Langevin thermostat. This cycle is repeated until a threshold distance is reached or other user-defined termination criteria are met.