Force probe molecular dynamics simulations.

Many proteins are molecular nano-machines, which perform their biological function via well-coordinated structural transitions. Often, these motions occur on much slower time scales than those accessible to conventional molecular dynamics techniques, which are limited to submicrosecond time scales by current computer technology. This is also true for ligand binding and unbinding reactions. Force probe simulations (or steered molecular dynamics) provide a powerful means to overcome this limitation, and thus to get insight into the atomistic mechanisms that underlie biological functions such as ligand binding. This chapter provides a basic introduction into this method. It further sketches a simple nonequilibrium statistical mechanics treatment that shows how to relate the results of force probe simulations to atomic force microscopy (AFM) or optical tweezer experiments. As an example, enforced unbinding simulations of streptavidin/biotin complexes are detailed.