Flesh out motivation to distinguish pathway vs. funnel in intro.

Also mention:
* difficulties comparing with molecular dynamics simulation.
* large span of ranges amoung available single molecule techniques.

diff --git a/src/introduction/main.tex b/src/introduction/main.tex
index f249e633d9673d1c0f5e4a77cf45707b74bd7502..17eee5dea36569f1a27b79c07d16c101535e01bd 100644 (file)
--- a/src/introduction/main.tex
+++ b/src/introduction/main.tex
@@ -96,6 +96,13 @@ explaining the folding mechanism.  For a number of years, the
   \end{center}
 \end{figure}
 
+When the choice of theoretical approach becomes murky, you must gather
+experimental data to help distinguish between similar models.
+Separating the pathway model from the funnel model is only marginally
+withing the realm of current experimental techniques, but with higher
+throughput and increased automation it should be easier to make such
+distinctions in the near future.
+
 
 \section{Single Molecule Protein Folding Studies}
 \label{sec:single-molecule}
@@ -114,18 +121,30 @@ averaging.  This provides important and complementary information
 about the functional mechanisms of several biological
 systems\citep{bustamante08}.
 
-% why AFM & what an AFM is
 Single molecule techniques provide an opportunity to study protein
 folding and unfolding at the level of a single molecule, where the
 distinction between the pathway model and funnel model is clearer.
-These techniques include optical measurements, \ie, single molecule
-fluorescence microscopy and spectroscopy, and mechanical manipulations
-of individual macromolecules, \ie, force microscopy and spectroscopy
-using atomic force microscopes (AFMs)%
-\nomenclature{AFM}{Atomic Force Microscope (or Microscopy)},
-laser tweezers\citep{forde02}, magnetic tweezers\citep{smith92},
-biomembrane force probes\citep{merkel99}, and centrifugal
-microscopes\citep{halvorsen09}.
+They also provide a convenient benchmark for verifying molecular
+dynamics simulations, because it takes a quite a bit of computing
+power to simulate even one biopolymer with anything close to atomic
+resolution over experimental timescales.  Even with significant
+computing resources, comparing molecular dynamics results with
+experimental data remains elusive.  For example, experimental pulling
+speeds are on the order of \bareU{$\mu$m/s}, while simulation pulling
+speeds are on the order of \bareU{m/s}\citep{zhao06}.
+
+% why AFM & what an AFM is
+Single molecule techniques for manipulating biopolymers include
+optical measurements, \ie, single molecule fluorescence microscopy and
+spectroscopy, and mechanical manipulations of individual
+macromolecules, \ie, force microscopy and spectroscopy using atomic
+force microscopes (AFMs), laser tweezers\citep{forde02}, magnetic
+tweezers\citep{smith92}, biomembrane force probes\citep{merkel99}, and
+centrifugal microscopes\citep{halvorsen09}.  These techniques cover a
+wide range of approaches, and even when the basic approach is the same
+(e.g.\ force microscopy), the different techniques span orders of
+magnitude in the range of their controllable parameters.
+\nomenclature{AFM}{Atomic Force Microscope (or Microscopy)}
 
 
 \section{Thesis Outline}