+
+\section{Review of current research}
+
+There is a long history of protein unfolding and unbinding
+simulations. Early work by \citet{grubmuller96} and
+\citet{izrailev97} focused on molecular dynamics (MD) simulations of
+receptor-ligand breakage. Around the same time, \citet{evans97}
+introduced a Monte Carlo Kramers' simulation in the context of
+receptor-ligand breakage. The approach pioneered by \citet{evans97}
+was used as the basis for analysis of the initial protein unfolding
+experiments\citep{rief97a}. However, none of these earlier
+implementations were open source, which made it difficult to reuse or
+validate their results.
+%
+\nomenclature[text ]{MD}{Molecular dynamics simulation. Simulate the
+ physical motion of atoms and molecules by numerically solving
+ Newton's equations.}
+
+Within the Monte Carlo simulation approach, there are two main models
+for protein domain unfolding under tension: Bell's and
+Kramers'\citep{schlierf06,hummer03,dudko06}. Bell introduced his
+model in the context of cell adhesion\citep{bell78}, but it has been
+widely used to model mechanical unfolding in
+proteins\citep{rief97a,carrion-vazquez99b,schlierf06} due to its
+simplicity and ease of use\citep{hummer03}
+(\cref{sec:sawsim:rate:bell}). Kramers introduced his theory in the
+context of thermally activated barrier crossings, which is how we use
+it here (\cref{sec:sawsim:rate:other}).
+
+Evans introduced the saddle-point Kramers' approximation in a protein
+unfolding context in 1997 (\xref{evans97}{equation}{3}). However,
+early work on mechanical unfolding focused on the simpler Bell
+model\citep{rief97a}. In the early 2000's, the
+saddle-point/steepest-descent approximation to Kramer's model
+(\xref{hanggi90}{equation}{4.56c}) was introduced into our
+field\citep{dudko03,hyeon03}. By the mid 2000's, the full-blown
+double-integral form of Kramer's model
+(\xref{hanggi90}{equation}{4.56b}) was in use\citep{schlierf06}.
+
+There have been some tangential attempts towards even fancier models:
+\citet{dudko03} attempted to reduce the restrictions of the
+single-unfolding-path model and \citet{hyeon03} attempted to measure
+the local roughness using temperature dependent unfolding. However,
+further work on these lines has been slow, because the Bell model fits
+the data well despite its simplicity. For more complicated transition
+rate models to gain ground, we need larger, more detailed datasets
+that expose features which the Bell model doesn't capture.