RECONSTRUCTING POTENTIAL-ENERGY FUNCTIONS FROM SIMULATED FORCE-INDUCED UNBINDING PROCESSES

One-dimensional stochastic models demonstrate that molecular dynamics simulations of a few nanoseconds can be used to reconstruct the essent ial features of the binding potential of macromolecules. This can be a ccomplished by inducing the unbinding with the help of external forces applied to the molecules, and discounting the irreversible work perfo rmed on the system by these forces. The fluctuation-dissipation theore m sets a fundamental limit on the precision with which the binding pot ential can be reconstructed by this method. The uncertainty in the res ulting potential is linearly proportional to the irreversible componen t of work performed on the system during the simulation. These results provide an a priori estimate of the energy barriers observable in mol ecular dynamics simulations.