2 ** Protein folding problem
3 ** Current approaches/state of the field as a whole
4 ** Single molecule techniques
6 **** Single molecule force spectroscopy
7 ***** Original force spectroscopy paper?
8 ***** Bustamante and lambda DNA (1994)
9 Demonstrates that labda DNA force-extension curves are well
10 modeled as WLCs, introducing WLCs in the context of force
12 ***** Evans and biotin/streptavidin (1997)
13 Unfolding and theory. Example on ligand-receptor binding.
14 ***** Rief and Titin (1997)
15 First force spectroscopy on a multi-globular single protein.
16 Reversible suggests unfolding of individual domains.
17 ***** Carrion-Vazquez review (2000)
18 Geometry argument for pulling angle irrelevance.
19 ***** Li review (2000)
20 Unfolding not due to pulling domains off the substrate surface.
21 ***** Carrion-Vazquez and I27 (1997)
22 First force spectroscopy on synthesized multi-globular I27.
23 Comparisons of unfolding constants with chemical techniques.
24 **** Temperature dependent unfolding
25 ***** Hyeon and Thirumalai (2003)
26 Extend Kramers' theory to determine energy landscape roughness.
27 ***** Yang and temperature control (2006)
28 Previous measurements on temperature dependent protein unfolding.
30 * Protein unfolding and related theories
33 ** Temperature and energy roughness
34 ** Jarzynsky's inequality
35 ** AFM cantilever calibration
37 *** Cantilever spring constant effect
39 pages 115--116 and Figure 2.a
41 Discusses energy landscape curvature and rebinding effects.
42 (Aha, this is what Noy wanted me to talk about).
43 **** Walton et al. 2008
44 Biophys J, 94 (2008), 7 2621--2630.
48 E** = E(x) - Fx + ½kx²
50 k_off = k₀ exp([F_R - ½kx_b]/F_b)
52 Competetion between number of parallel unfolders and effective
53 loading rate. The unfolding rate must be binned somehow, and the
54 scaffold effect makes binning difficult.
56 = unfolding rate of proteins present within Delta F of an
57 average tension F applied via a linker of stiffness
58 kappa=dF/dx (kappa to deal with the
59 [[Cantilever spring constant effect]].
60 I suggest we use the censored survival statistics common to
61 medical studies, and hopefully see exponential decay for each
62 force. We'll probably have to lump similar loading rates
63 (=kappa∙v) together, and the more gently loaded proteins will
64 survive longer (having a lower mean force after the same length of
65 time in the [F, F+Delta F] bin). The general trend will also be
66 towards accelerated exponential decay, since the mean forces of
67 all proteins will increase throughout the bin.
68 **** Zinober et al. 2002
69 Protein Science, 11 (2002), 12 2759--2765.
70 Monte Carlo simulation and experiment on I27 and mutants.
71 **** Censored survival statistics, Kaplan-Meier
72 ***** Kaplan, E.L. & Meier, P. 1958
73 "Nonparametric estimation from incomplete observations," Journal
74 of the American Statistical Association, 53, 457-481 (1958).
75 ***** Chris Barker 2009
76 "The Mean, Median, and Confidence Intervals of the Kaplan-Meier
77 Survival Estimate—Computations and Applications," The American
78 Statistician, 63(1), 78--80 (2009). DOI 10.1198/tast.2009.0015
79 ***** Newcombe, Robert G. 1998
80 "Two-Sided Confidence Intervals for the Single Proportion:
81 Comparison of Seven Methods," Statistics in Medicine, 17,
83 ***** Wilson, E. B. 1927
84 "Probable Inference, the Law of Succession, and Statistical
85 Inference," Journal of the American Statistical Association, 22,
87 ***** Greenwood, M. 1926
88 "The natural duration of cancer." Reports on Public Health and
89 Medical Subjects 33, 1–26. Her Majesty’s Stationery Office, London.
90 ***** Meeker, W.Q., and Escobar, L.A. 1998
91 "Statistical Methods for Reliability Data", John Wiley & Sons,
93 Greenwood's formula for Kaplan-Meier error. Example calculations:
94 http://www.weibull.com/LifeDataWeb/nonparametric_analysis.htm
96 ** Temperature dependent energy landscape roughness
97 ** Effect of cantilever stiffness on unfolding behavior
99 ** Experiment control/analysis software
101 * Summary/future directions