Simulating the dynamic strength of molecular interactions

It has been demonstrated that the force at which an interaction will break depends on the rate at which force is applied. Here, we present a strategy for the modeling of the forced dissociation of a ligand-receptor interactio n, using the streptavidin-biotin complex as an example, over a range of loa ding rates that are outside those attainable by current all-atom simulation techniques. The method adopted is a combination of traditional reaction co ordinate mapping and Brownian dynamics. Our simulations predict a dynamic f orce spectrum for the streptavidin-biotin interaction of similar form to re cent experimental results. In this study we confirm the logarithmic depende nce of a rupture force on the loading rate, highlight the barriers that are probed at the loading rates attainable by the atomic force microscope, and discuss how these barriers transform under loading. Furthermore, it is con firmed that additional information obtained from the distribution of ruptur e forces can be used to complement dynamic force spectroscopy data and shou ld be used in experimental studies to verify the results obtained. (C) 2001 American Institute of Physics.