introduction/main.tex: Add 'Why unfolding?' section

diff --git a/src/introduction/main.tex b/src/introduction/main.tex
index 51b29e18784cd3673485c2f36c044ab2991b722d..8d0b1076d819161feb31d8a3439474285ed69b2e 100644 (file)
--- a/src/introduction/main.tex
+++ b/src/introduction/main.tex
@@ -12,8 +12,11 @@ developing drugs targeting biologically significant receptors and
 enzymes.  In this chapter, I describe the protein folding problem in a
 general sense (\cref{sec:folding-problem}), discuss theoretical
 frameworks for understanding protein folding
-(\cref{sec:energy-landscape}), and highlight the role of SMFS in
-extending this understanding (\cref{sec:single-molecule}).
+(\cref{sec:energy-landscape}), highlight the role of SMFS in extending
+this understanding (\cref{sec:single-molecule}), and explain the roll
+of unfolding experiments in understanding protein folding
+(\cref{sec:unfolding}).  The last section in this chapter gives a
+roadmap for the rest of the thesis (\cref{sec:outline}).
 
 \section{The Protein Folding Problem}
 \label{sec:folding-problem}
@@ -166,6 +169,38 @@ of approaches, and even when the basic approach is the same
 magnitude in the range of their controllable parameters.
 \nomenclature{AFM}{Atomic Force Microscope (or Microscopy)}
 
+\section{Why \emph{unfolding?}}
+\label{sec:unfolding}
+
+There's a lot of talk about protein \emph{folding} in this chapter,
+while the rest of the thesis (and the title) are about
+\emph{unfolding}.  If you understand protein folding, you can use your
+understanding to design drugs with a particular conformation, or
+predict the conformation of a biologically important receptor
+(\cref{sec:folding-problem}).  Understanding protein unfolding is less
+directly useful, because unfolded proteins are rarely biologically
+relevant (although it does happen\cref{TODO}).
+
+The focus on unfolding is mainly because it's easier to unravel
+proteins by pulling on their ends (\cref{sec:procedure}) than it is to
+fold them into their native state by pushing on those ends
+(\cref{fig:ligand-receptor,fig:I27}).  For proteins with smooth enough
+energy landscapes, the folding and unfolding routes will be similar,
+so knowledge about the unfolding behavior \emph{does} shed light on
+the folding behavior.
+
+Practically, the distinction between folding and unfolding makes
+little difference, as drug designers and doctors are not consuming
+SMFS results directly.  For researchers calibrating molecular dynamics
+simulations, it doesn't matter if you compare simulated folding
+experiments with experimental folding experiments, or simulated
+unfolding experiments with experimental unfolding experiments.  The
+important thing is to compare your simulation against \emph{some}
+experimental benchmarks.  If your molecular dynamics simulation
+successfully predicts a protein's unfolding behavior, it makes me more
+confident that it will correctly predict the protein's native folding
+behavior.
+
 
 \section{Thesis Outline}
 \label{sec:outline}