From: W. Trevor King Date: Wed, 2 Dec 2009 07:51:22 +0000 (-0500) Subject: Began versioning X-Git-Tag: v1.0~471 X-Git-Url: http://git.tremily.us/?a=commitdiff_plain;h=8d8e6ad6275ce93bed08b2fd33ce46ccb04054fa;p=thesis.git Began versioning --- 8d8e6ad6275ce93bed08b2fd33ce46ccb04054fa diff --git a/outline.org b/outline.org new file mode 100644 index 0000000..2b02850 --- /dev/null +++ b/outline.org @@ -0,0 +1,101 @@ +* Introduction +** Protein folding problem +** Current approaches/state of the field as a whole +** Single molecule techniques +*** Literature review +**** Single molecule force spectroscopy +***** Original force spectroscopy paper? +***** Bustamante and lambda DNA (1994) + Demonstrates that labda DNA force-extension curves are well + modeled as WLCs, introducing WLCs in the context of force + spectroscopy. +***** Evans and biotin/streptavidin (1997) + Unfolding and theory. Example on ligand-receptor binding. +***** Rief and Titin (1997) + First force spectroscopy on a multi-globular single protein. + Reversible suggests unfolding of individual domains. +***** Carrion-Vazquez review (2000) + Geometry argument for pulling angle irrelevance. +***** Li review (2000) + Unfolding not due to pulling domains off the substrate surface. +***** Carrion-Vazquez and I27 (1997) + First force spectroscopy on synthesized multi-globular I27. + Comparisons of unfolding constants with chemical techniques. +**** Temperature dependent unfolding +***** Hyeon and Thirumalai (2003) + Extend Kramers' theory to determine energy landscape roughness. +***** Yang and temperature control (2006) + Previous measurements on temperature dependent protein unfolding. +** Goals +* Protein unfolding and related theories +** Bell's model +** Kramer's model +** Temperature and energy roughness +** Jarzynsky's inequality +** AFM cantilever calibration +** Sources of error +*** Cantilever spring constant effect +**** Evans, 2001 + pages 115--116 and Figure 2.a + + Discusses energy landscape curvature and rebinding effects. + (Aha, this is what Noy wanted me to talk about). +**** Walton et al. 2008 + Biophys J, 94 (2008), 7 2621--2630. + + Energy landscape E + E* = E(x) + ½kx² + E** = E(x) - Fx + ½kx² + F_b = x_b/k_B T + k_off = k₀ exp([F_R - ½kx_b]/F_b) +*** Scaffold effect + Competetion between number of parallel unfolders and effective + loading rate. The unfolding rate must be binned somehow, and the + scaffold effect makes binning difficult. + k(F,Delta F,kappa) + = unfolding rate of proteins present within Delta F of an + average tension F applied via a linker of stiffness + kappa=dF/dx (kappa to deal with the + [[Cantilever spring constant effect]]. + I suggest we use the censored survival statistics common to + medical studies, and hopefully see exponential decay for each + force. We'll probably have to lump similar loading rates + (=kappa∙v) together, and the more gently loaded proteins will + survive longer (having a lower mean force after the same length of + time in the [F, F+Delta F] bin). The general trend will also be + towards accelerated exponential decay, since the mean forces of + all proteins will increase throughout the bin. +**** Zinober et al. 2002 + Protein Science, 11 (2002), 12 2759--2765. + Monte Carlo simulation and experiment on I27 and mutants. +**** Censored survival statistics, Kaplan-Meier +***** Kaplan, E.L. & Meier, P. 1958 + "Nonparametric estimation from incomplete observations," Journal + of the American Statistical Association, 53, 457-481 (1958). +***** Chris Barker 2009 + "The Mean, Median, and Confidence Intervals of the Kaplan-Meier + Survival Estimate—Computations and Applications," The American + Statistician, 63(1), 78--80 (2009). DOI 10.1198/tast.2009.0015 +***** Newcombe, Robert G. 1998 + "Two-Sided Confidence Intervals for the Single Proportion: + Comparison of Seven Methods," Statistics in Medicine, 17, + 857-872 (1998). +***** Wilson, E. B. 1927 + "Probable Inference, the Law of Succession, and Statistical + Inference," Journal of the American Statistical Association, 22, + 209-212 (1927). +***** Greenwood, M. 1926 + "The natural duration of cancer." Reports on Public Health and + Medical Subjects 33, 1–26. Her Majesty’s Stationery Office, London. +***** Meeker, W.Q., and Escobar, L.A. 1998 + "Statistical Methods for Reliability Data", John Wiley & Sons, + Inc., New York, 1998. + Greenwood's formula for Kaplan-Meier error. Example calculations: + http://www.weibull.com/LifeDataWeb/nonparametric_analysis.htm +* Measurements +** Temperature dependent energy landscape roughness +** Effect of cantilever stiffness on unfolding behaviour +* Software +** Experiment control/analysis software +** Sawsim +* Summary/future directions