There are two typical protocols of SMD: one in which pulling velocity is held constant and one in which applied force is constant. Typically, part of the studied system (e.g. an atom in a protein) is restrained by a harmonic potential. Forces are then applied to specific atoms at either a constant velocity or a constant force. Umbrella sampling is used to move the system along the desired reaction coordinate by varying, for example, the forces, distances, and angles manipulated in the simulation. Through umbrella sampling, all of the system's configurations—both high-energy and low-energy—are adequately sampled. Then, each configuration's change in free energy can be calculated as the potential of mean force.[41] A popular method of computing PMF is through the weighted histogram analysis method (WHAM), which analyzes a series of umbrella sampling simulations