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Protein Folding
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We use two simple models and the energy landscape perspective to study protein folding kinetics. A major challenge has been to use the landscape perspective to interpret experimental data, which requires ensemble averaging over the microscopic trajectories usually observed in such models. Here, because of the simplicity of the model, this can be achieved. The kinetics of protein folding falls into two classes: multiple-exponential and two-state (single-exponential) kinetics. Experiments show that two-state relaxation times have "chevron plot" dependences on temperature. We find that HP and HP+ models can account for these behaviors. The HP model often gives bumpy landscapes with many kinetic traps and multiple-exponential behavior, whereas the HP+ model gives more smooth funnels and two-state behavior. Multiple-exponential kinetics often involves fast collapse into kinetic traps and slower barrier climbing out of the traps. Two-state kinetics often involves entropic barriers where conformational searching limits the folding speed. Transition states and activation barriers need not define a single conformation; they can involve a broad ensemble of the conformations searched on the way to the native state. We find that unfolding is not always a direct reversal of the folding process. Proteins 30:2-33, 1998.
Here are some figures I produced for Hue Sun Chan (chan@maxwell.ucsf.edu) and Ken A. Dill's (dill@maxwell.ucsf.edu) paper Protein Folding in the Landscape Perspective: Chevron Plots and Non-Arrhenius Kinetics in Proteins: Structure, Function, and Genetics, Volume 30 number 1, January 1998, pp. 2--33. You're welcome to download and reuse them, provided you cite the paper.
The figures are either compressed (gnuzip) PostScript files, or jpeg. Most graphical browsers can display jpeg files. You might need to tinker with your browser to display the PostScript files, but they should give superior resolution once you download them. If you have problems with the file format, let's talk: lsch@maxwell.ucsf.edu.
There's a Mac version of gnuzip at MacGzip, and one for DOS at DOS gnuzip. However ... to unzip that file, you'll need unzip DOS unzip. The wonders of GNU (and other) free software, eh!
Page maintainer, Danny Heap, can be reached at lsch@maxwell.ucsf.edu. Last update: March 1998