tags/papersunfolding disastershttp://www.physics.drexel.edu/~wking/unfolding-disasters/tags/papers/unfolding disastersikiwiki2011-04-22T10:56:19ZResearchhttp://www.physics.drexel.edu/~wking/unfolding-disasters/posts/Research/2010-11-18T18:04:02Z2010-11-18T18:04:02Z
<p>My current work for <a href="http://www.physics.drexel.edu/~gyang/">Prof. Yang</a> involves unfolding proteins using
an Atomic Force Microscope (AFM) at different temperatures to estimate
the roughness of their free energy landscape. For a brief overview of
force spectroscopy, see my <a href="http://www.physics.drexel.edu/~wking/unfolding-disasters/tags/papers/../../posts/Force_spectroscopy/">two second
summary</a>. For more detail, you can look at some of
my <span class="selflink">papers</span>.</p>
<p>I've written some <span class="createlink">experimental control software</span>, a
Monte Carlo simulation program (<a href="http://www.physics.drexel.edu/~wking/unfolding-disasters/tags/papers/../../posts/sawsim/">sawsim</a>) for analyzing the
unfolding sawtooth curves, as well as software for calibrating AFM
cantilevers via the thermal tune method (<a href="http://www.physics.drexel.edu/~wking/unfolding-disasters/tags/papers/../../posts/calibcant/">calibcant</a>), scaling the
unfolding data, selecting good curves, and fitting those curves with
wormlike chains (<a href="http://www.physics.drexel.edu/~wking/unfolding-disasters/tags/papers/../../posts/Hooke/">Hooke</a>).</p>
<p>Along the way I've had to learn way too much about the internal
workings of our <a href="http://www.physics.drexel.edu/~wking/unfolding-disasters/tags/papers/../../posts/MultiMode/">MultiMode</a> AFM.</p>
<p>I've also posted my notes for our <a href="http://www.physics.drexel.edu/~wking/unfolding-disasters/tags/papers/../../posts/Abax/">Debian cluster</a>.</p>
Thesishttp://www.physics.drexel.edu/~wking/unfolding-disasters/posts/Thesis/2010-11-17T12:26:28Z2010-11-17T12:26:28Z
<p><span class="infobox">
Available in a <a href="http://www.physics.drexel.edu/~wking/unfolding-disasters/tags/papers/../git/">git</a> repository.<br />
Repository: <a href="http://www.physics.drexel.edu/~wking/code/git/gitweb.cgi?p=thesis.git" rel="vcs-git" title="thesis repository">thesis</a><br />
Author: W. Trevor King<br />
</span></p>
<p>The source for my Ph.D. thesis (in progress). A <a href="http://www.physics.drexel.edu/~wking/unfolding-disasters/tags/papers/../../posts/Thesis/draft.pdf">draft</a>
is compiled after each commit. I use the <a href="http://www.physics.drexel.edu/~wking/unfolding-disasters/tags/papers/../../posts/drexel-thesis/">drexel-thesis</a> class,
which I also maintain.</p>
<p>Exciting features: <span class="createlink">SCons</span> build; <a href="http://www.physics.drexel.edu/~wking/unfolding-disasters/tags/papers/../../posts/Asymptote/">Asymptote</a>/asyfig, <a href="http://www.physics.drexel.edu/~wking/unfolding-disasters/tags/papers/../../posts/PGF/">PGF</a>, and
<a href="http://www.pymol.org/">PyMOL</a> figures.</p>
sawsimhttp://www.physics.drexel.edu/~wking/unfolding-disasters/posts/sawsim/2011-04-22T10:56:19Z2010-10-23T18:08:02Z
<p><span class="infobox">
Available in a <a href="http://www.physics.drexel.edu/~wking/unfolding-disasters/tags/papers/../git/">git</a> repository.<br />
Repository: <a href="http://www.physics.drexel.edu/~wking/code/git/gitweb.cgi?p=sawsim.git" rel="vcs-git" title="sawsim repository">sawsim</a><br />
Author: W. Trevor King<br />
</span></p>
<h1>Introduction</h1>
<p>My <a href="http://www.physics.drexel.edu/~wking/unfolding-disasters/tags/papers/../../posts/Thesis/">thesis</a> project investigates protein unfolding via the
experimental technique of <a href="http://www.physics.drexel.edu/~wking/unfolding-disasters/tags/papers/../../posts/Force_spectroscopy/">force spectroscopy</a>. In force
spectroscopy, we mechanically stretch chains of proteins, usually by
pulling one end of the chain away from a surface with an <a href="http://en.wikipedia.org/wiki/Atomic_force_microscopy">AFM</a>.</p>
<p>For velocity clamp experiments (the simplest to carry out
experimentally), the experiments produce "sawtooth" force-displacement
curves. As the protein stretches, the tension increases. At some
point, a protein domain unfolds, increasing the total length of the
chain and relaxing the tension. As we continue to stretch the
protein, we see a series of unfolding peaks. The <span class="createlink">GPLed</span>
program <a href="http://www.physics.drexel.edu/~wking/unfolding-disasters/tags/papers/../../posts/Hooke/">Hooke</a> analyzes the sawtooth curves and extracts lists of
unfolding forces.</p>
<p>Lists of unfolding forces are not particularly interesting by
themselves. The most common approach for extracting some physical
insights from the unfolding curves is to take a guess at an
explanatory model and check the predicted behavior of the model
against the measured behavior of the protein. If the model does a
good job of explaining the protein behavior, it might be what's
actually going on behind the scenes. Sawsim is my (<a href="http://dx.doi.org/10.1016/j.ijbiomac.2009.12.001">published</a>!)
tool for simulating force spectroscopy experiments and matching the
simulations to experimental results.</p>
<p>The main benefits of sawsim are its ability to simulate systems with
arbitrary numbers of states (see the <a href="http://www.physics.drexel.edu/~wking/unfolding-disasters/tags/papers/../../posts/sawsim/sawsim.pdf">manual</a>) and to
easily compare the simulated data with experimental values. The
following figure shows a long valley of reasonable fits to some
ubiquitin unfolding data. See the IJBM paper (linked above) for more
details.</p>
<p><a href="http://www.physics.drexel.edu/~wking/unfolding-disasters/tags/papers/../../posts/sawsim/fit-space.png"><img src="http://www.physics.drexel.edu/~wking/unfolding-disasters/tags/papers/../../posts/sawsim/fit-space.png" width="1063" height="709" alt="Fit space Surface bump for photodiode sensitivity" title="Surface bump for photodiode sensitivity" class="img" /></a></p>
<h1>Getting started</h1>
<p>Sawsim should run anywhere you have a C compiler and Python 2.5+.
I've tested it on Gentoo and Debian, and I've got an ebuild in my
<a href="http://www.physics.drexel.edu/~wking/unfolding-disasters/tags/papers/../../posts/Gentoo_overlay/">Gentoo overlay</a>. It should also run fine on Windows, etc., but I
don't have access to any Windows boxes with a C compiler, so I haven't
tested that (<a href="http://www.physics.drexel.edu/~wking/unfolding-disasters/tags/papers/../../contact/">email me</a> if you have access to such a machine
and want to try installing Sawsim).</p>
<p>See the <a href="http://www.physics.drexel.edu/~wking/unfolding-disasters/tags/papers/../../posts/sawsim/README/">README</a>, <a href="http://www.physics.drexel.edu/~wking/unfolding-disasters/tags/papers/../../posts/sawsim/sawsim.pdf">manual</a>, and <a href="http://pypi.python.org/pypi/pysawsim/">PyPI page</a> for
more details.</p>