3 @string{IJBMM = "International Journal of Biological Macromolecules"}
4 @string{SCI = "Science"}
8 @string{Drexel = "Drexel University"}
12 @string{DrexelPhysics = "Department of Physics, Drexel University, 3141
13 Chestnut Street, Philadelphia, PA 19104, USA."}
17 @string{WKing = "King, W.~Trevor"}
19 @string{JFernandez = "Fernandez, Julio M."}
20 @string{HEGaub = "Gaub, Hermann E."}
21 @string{MGautel = "Gautel, Mathias"}
22 @string{FOesterhelt = "Oesterhelt, Filipp"}
23 @string{MRief = "Rief, Matthias"}
24 @string{MSu = "Su, Meihong"}
25 @string{GYang = "Yang, Guoliang"}
31 title = "Open source single molecule force spectroscopy",
35 address = DrexelPhysics,
36 url = "http://hdl.handle.net/1860/4188",
37 eprint = "http://dspace.library.drexel.edu/bitstream/1860/4188/1/King_WilliamPhD.pdf",
38 keywords = "Physics; Molecular spectroscopy; Biophysics",
39 abstract = "Single molecule force spectroscopy (SMFS) experiments
40 provide an experimental benchmark for testing simulated and
41 theoretical predictions of protein unfolding behavior.
42 Despite it use since 1997\citep{rief97a}, the labs currently
43 engaged in SMFS use in-house software and procedures for
44 critical tasks such as cantilever calibration and Monte Carlo
45 unfolding simulation. Besides wasting developer time
46 producing and maintaining redundant implementations, the lack
47 of transparency makes it more difficult to share data and
48 techniques between labs, which slows progress. In some cases
49 it can also lead to ambiguity as to which of several similar
50 approaches, correction factors, etc.\ were used in a
54 In this thesis, I introduce an SMFS sofware suite for
55 cantilever calibration
56 (\href{https://pypi.python.org/pypi/calibcant/}{calibcant}),
58 (\href{https://pypi.python.org/pypi/unfold-protein}{unfold-protein}),
59 analysis (\href{https://pypi.python.org/pypi/Hooke}{Hooke}),
61 (\href{http://blog.tremily.us/posts/sawsim/}{sawsim}) in the
62 context of velocity clamp unfolding of I27 octomers in buffers
63 with varying concentrations of \CaCl\textsubscript{2}. All of
64 the tools are licensed under open source licenses, which
65 allows SMFS researchers to centralize future development.
66 Where possible, care has been taken to keep these packages
67 operating system (OS) agnostic. The experiment logic in
68 unfold-protein and calibcant is still nominally OS agnostic,
69 but those packages depend on
70 \href{https://pypi.python.org/pypi/pyafm}{more fundamental
71 packages} that control the physical hardware in use. At the
72 bottom of the physical-interface stack are the
73 \href{http://www.comedi.org/}{Comedi} drivers from the Linux
74 kernel. Users running other operating systems should be able
75 to swap in analogous low level physical-interface packages if
76 Linux is not an option.",
80 author = WKing #" and "# MSu #" and "# GYang,
81 title = "{M}onte {C}arlo simulation of mechanical unfolding of proteins
82 based on a simple two-state model",
86 address = DrexelPhysics,
92 alternative_issn = "1879-0003",
93 doi = "10.1016/j.ijbiomac.2009.12.001",
94 url = "http://www.sciencedirect.com/science/article/B6T7J-
95 4XWMND2-1/2/7ef768562b4157fc201d450553e5de5e",
97 keywords = "Atomic force microscopy;Mechanical unfolding;Monte Carlo
98 simulation;Worm-like chain;Single molecule methods",
99 abstract = "Single molecule methods are becoming routine biophysical
100 techniques for studying biological macromolecules. In mechanical
101 unfolding of proteins, an externally applied force is used to induce
102 the unfolding of individual protein molecules. Such experiments have
103 revealed novel information that has significantly enhanced our
104 understanding of the function and folding mechanisms of several types
105 of proteins. To obtain information on the unfolding kinetics and the
106 free energy landscape of the protein molecule from mechanical unfolding
107 data, a Monte Carlo simulation based on a simple two-state kinetic
108 model is often used. In this paper, we provide a detailed description
109 of the procedure to perform such simulations and discuss the
110 approximations and assumptions involved. We show that the appearance of
111 the force versus extension curves from mechanical unfolding of proteins
112 is affected by a variety of experimental parameters, such as the length
113 of the protein polymer and the force constant of the cantilever. We
114 also analyze the errors associated with different methods of data
115 pooling and present a quantitative measure of how well the simulation
116 results fit experimental data. These findings will be helpful in
117 experimental design, artifact identification, and data analysis for
118 single molecule studies of various proteins using the mechanical
124 @unpublished{ 2013-05-thesis,
125 title= {Open source single molecule force spectroscopy},
130 note= {Thesis defense, Drexel University},
131 address = {Drexel University},
132 url = {http://blog.tremily.us/posts/Thesis/talk/},
135 @unpublished{ 2013-01-columbia,
136 title= {Collaborative version control with {G}it},
140 note= {Software Carpentry boot camp, Columbia University},
141 address = {Columbia University},
144 @unpublished{ 2009-10-life-cycles,
145 title= {Software life-cycles and alphabet soup},
149 note= {Drexel Physics Graduate Student Association},
150 address = {Drexel University}
153 @unpublished{ 2008-06-locks,
154 title= {Manipulating combination locks \& Ray tracing with polarization},
158 note= {Drexel Physics Graduate Student Association},
159 address = {Drexel University}
162 @unpublished{ 2006-05-quantum-computing,
163 title= {Quantum Computing},
166 note= {Rochester Solid State final},
167 address = {University of Rochester}
173 @unpublished{ 2013-04-swc,
174 title= {Teaching Software Carpentry: Better Science through Science},
178 note= {Drexel CoAS Research Day},
179 address = {Philadelphia, Pennsylvania},
182 @unpublished{ 2012-04-calibcant,
183 title= {Thermally calibrating {AFM} cantilever spring constants},
187 note= {Drexel CoAS Research Day},
188 address = {Philadelphia, Pennsylvania},
191 @unpublished{ 2011-04-saswsim,
192 title= {Flexible parallel simulations and packaging},
196 note= {Drexel CoAS Research Day},
197 address = {Philadelphia, Pennsylvania},
200 @unpublished{ 2010-04-open-source,
201 title= {Open source software in experimental protein unfolding},
205 note= {Drexel CoAS Research Day},
206 address = {Philadelphia, Pennsylvania},
209 @unpublished{ 2009-03-roughness,
210 title= {Experimental Estimation of the Free Energy Landscape
211 Roughness of Protein Molecules},
215 note= {Biophysical Society Annual Meeting},
216 address = {Philadelphia, Pennsylvania},
219 @unpublished{ 2008-04-sawsim,
220 title= {Simulated mechanical unfolding of single proteins},
224 note= {Drexel CoAS Research Day},
225 address = {Philadelphia, Pennsylvania},
228 @unpublished{ 2008-02-stiffness,
229 title= {Effects of Cantilever Stiffness on Unfolding Force in AFM
234 note= {Biophysical Society Annual Meeting},
235 address = {Long Beach, California},
241 author = MRief #" and "# MGautel #" and "# FOesterhelt #" and "# JFernandez
243 title = "Reversible Unfolding of Individual Titin Immunoglobulin Domains by
249 pages = "1109--1112",
250 doi = "10.1126/science.276.5315.1109",
251 eprint = "http://www.sciencemag.org/cgi/reprint/276/5315/1109.pdf",
252 url = "http://www.sciencemag.org/cgi/content/abstract/276/5315/1109",
253 note = "Seminal paper for force spectroscopy on Titin.",