  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 1.4 s (3.4 E13 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.
