%0 Journal Article %1 Dickson2011NEUSRNA %A Dickson, Alex %A Maienschein-Cline, Mark %A Tovo-Dwyer, Allison %A Hammond, Jeff R. %A Dinner, Aaron R. %D 2011 %J Journal of Chemical Theory and Computation %K enhanced-sampling non-equilibrium-statistical-mechanics non-equilibrium-umbrella-sampling umbrella-sampling %N 9 %P 2710-2720 %R 10.1021/ct200371n %T Flow-Dependent Unfolding and Refolding of an RNA by Nonequilibrium Umbrella Sampling %U http://dx.doi.org/10.1021/ct200371n %V 7 %X Nonequilibrium experiments of single biomolecules such as force-induced unfolding reveal details about a few degrees of freedom of a complex system. Molecular dynamics simulations can provide complementary information, but exploration of the space of possible configurations is often hindered by large barriers in phase space that separate metastable regions. To solve this problem, enhanced sampling methods have been developed that divide a phase space into regions and integrate trajectory segments in each region. These methods boost the probability of passage over barriers and facilitate parallelization since integration of the trajectory segments does not require communication, aside from their initialization and termination. Here, we present a parallel version of an enhanced sampling method suitable for systems driven far from equilibrium: nonequilibrium umbrella sampling (NEUS). We apply this method to a coarse-grained model of a 262-nucleotide RNA molecule that unfolds and refolds in an explicit flow field modeled with stochastic rotation dynamics. Using NEUS, we are able to observe extremely rare unfolding events that have mean first passage times as long as 45 s (1.1 × 1015 dynamics steps). We examine the unfolding process for a range of flow rates of the medium, and we describe two competing pathways in which different intramolecular contacts are broken.

@article{Dickson2011NEUSRNA, abstract = { Nonequilibrium experiments of single biomolecules such as force-induced unfolding reveal details about a few degrees of freedom of a complex system. Molecular dynamics simulations can provide complementary information, but exploration of the space of possible configurations is often hindered by large barriers in phase space that separate metastable regions. To solve this problem, enhanced sampling methods have been developed that divide a phase space into regions and integrate trajectory segments in each region. These methods boost the probability of passage over barriers and facilitate parallelization since integration of the trajectory segments does not require communication, aside from their initialization and termination. Here, we present a parallel version of an enhanced sampling method suitable for systems driven far from equilibrium: nonequilibrium umbrella sampling (NEUS). We apply this method to a coarse-grained model of a 262-nucleotide RNA molecule that unfolds and refolds in an explicit flow field modeled with stochastic rotation dynamics. Using NEUS, we are able to observe extremely rare unfolding events that have mean first passage times as long as 45 s (1.1 × 1015 dynamics steps). We examine the unfolding process for a range of flow rates of the medium, and we describe two competing pathways in which different intramolecular contacts are broken. }, added-at = {2017-02-15T23:25:09.000+0100}, author = {Dickson, Alex and Maienschein-Cline, Mark and Tovo-Dwyer, Allison and Hammond, Jeff R. and Dinner, Aaron R.}, biburl = {https://www.bibsonomy.org/bibtex/2912e545433236adf1729b70beb1d4ca2/salotz}, description = {Flow-Dependent Unfolding and Refolding of an RNA by Nonequilibrium Umbrella Sampling - Journal of Chemical Theory and Computation (ACS Publications)}, doi = {10.1021/ct200371n}, eprint = {http://dx.doi.org/10.1021/ct200371n}, interhash = {c2d6419149514b4ebac3a48c4a58c016}, intrahash = {912e545433236adf1729b70beb1d4ca2}, journal = {Journal of Chemical Theory and Computation}, keywords = {enhanced-sampling non-equilibrium-statistical-mechanics non-equilibrium-umbrella-sampling umbrella-sampling}, note = {PMID: 26605464}, number = 9, pages = {2710-2720}, timestamp = {2017-02-15T23:25:09.000+0100}, title = {Flow-Dependent Unfolding and Refolding of an RNA by Nonequilibrium Umbrella Sampling}, url = {http://dx.doi.org/10.1021/ct200371n}, volume = 7, year = 2011 }