Before revision: The computation of dissociation rates from modeling of macromolecule-ligand unbinding processes is a topic of recent and increasing interest for drug design applications. However, the complexity of the high-dimensional space explored during dissociation on timescales that often exceed those accessible to conventional molecular dynamics (MD) simulations make this task highly challenging.
After revision: The protein-ligand residence time, tau, influences molecular function in biological networks and has been recognized as an important determinant of drug efficacy. To predict tau, computational methods must overcome the problem that tau often exceeds the timescales accessible to conventional molecular dynamics (MD) simulations make this task highly challenging.