  While seemingly straightforward in principle, the reliable estimation of rate
constants is seldom easy in practice. Numerous issues, such as the complication
of poor reaction coordinates, cause obvious approaches to yield unreliable
estimates. When a reliable order parameter is available, the reactive flux
theory of Chandler allows the rate constant to be extracted from the plateau
region of an appropriate reactive flux function. However, when applied to real
data from single-molecule experiments or molecular dynamics simulations, the
rate can sometimes be difficult to extract due to the numerical differentiation
of a noisy empirical correlation function or difficulty in locating the plateau
region at low sampling frequencies. We present a modified version of this
theory which does not require numerical derivatives, allowing rate constants to
be robustly estimated from the time-correlation function directly. We compare
these approaches using single-molecule force spectroscopy measurements of an
RNA hairpin.
