Unlike docking, MD simulations resolve-in full atomistic detail-the overall dynamics of the protein-ligand system by solving Newton's equations of motions in discrete timesteps. This can get very computationally expensive if one wants to simulate biological timescales as MD simulations must take timesteps which are constrained by the fastest motion in the system (e.g. bond vibrations at 1-2 femtoseconds). One may use schemes like hydrogen mass re-partitioning to enable one to take longer timesteps (e.g. 4fs) by slowing down hydrogen bond stretching, but interesting biological motions occur at much larger timescales necessitating large numbers of timesteps and great computational cost. Interesting biological motions like protein folding or other large conformational changes have timescales ranges from 10 -6 s (µs) to 10 0 s or even longer, requiring extremely long compute times if one aims to capture these types of motions.