We introduce a rigorous and powerful method to microscopically compute the observables which characterize the thermodynamics and kinetics of rare macromolecular transitions  . In order to sample the ensemble of statistically significant reaction pathways, we define a biased molecular dynamics (MD) in which barrier-crossing transitions are accelerated without introducing any unphysical external force. In contrast to other biased MD methods, in the present approach the systematic errors which are generated in order to accelerate the transition can be analytically calculated and therefore can be corrected for. This allows for an accurate and computationally very efficient reconstruction of the free-energy profile as a function of an arbitrarily chosen reaction coordinate . The transition path time can then be readily evaluated within the Dominant Reaction Pathways (DRP) approach. We illustrate and test this method on a simple system and show that it yields very accurate results .
We introduce a rigorous method to microscopically compute the observables which characterize the thermodynamics and kinetics of rare macromolecular transitions for which it is possible to identify a priori a slow reaction coordinate . In order to sample the ensemble of statistically significant reaction pathways, we define a biased molecular dynamics (MD) in which barrier-crossing transitions are accelerated without introducing any unphysical external force. In contrast to other biased MD methods, in the present approach the systematic errors which are generated in order to accelerate the transition can be analytically calculated and therefore can be corrected for. This allows for a computationally efficient reconstruction of the free-energy profile as a function of the reaction coordinate and for the calculation of the corresponding diffusion coefficient . The transition path time can then be readily evaluated within the Dominant Reaction Pathways (DRP) approach. We illustrate and test this method by characterizing a thermally activated transition on a two-dimensional energy surface and the folding of a small protein fragment within a coarse-grained model .
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for which it is possible to identify a priori a slow reaction coordinate
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an accurate and computationally very
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an arbitrarily chosen reaction coordinate
the reaction coordinate and for the calculation of the corresponding diffusion coefficient
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on a simple system and show that it yields very accurate results
by characterizing a thermally activated transition on a two-dimensional energy surface and the folding of a small protein fragment within a coarse-grained model