Additional modules
Simulating CPMG and CEST profiles
ChemEx allows simulating CPMG or CEST profiles based on a given set of input parameters. Such simulations may be useful to learn about the effects of each individual parameter on the final results.
A typical command for simulation purposes with ChemEx is like this:
chemex simulate -e <FILE> \
-p <FILE> \
-d <MODEL> \
-o <DIR>
Example simulation results for CPMG and CEST experiments are shown below:
Options
| Option | Description |
|---|---|
-e, --experiments | Specify the files containing experimental setup and data location |
-p, --parameters | Specify the files containing the initial values of fitting parameters |
-d, --model | Specify the exchange model used to fit the datasets (default: 2st) |
-o, --output | Specify the output directory (default: ./Output) |
--plot {nothing,normal} | Plotting level (default: normal) |
--include | Residue(s) to include in the fit (optional) |
--exclude | Residue(s) to exclude from the fit (optional) |
Example
An example use of the module is available
here
with the script simulate.sh.
Plotting best-fit parameters
ChemEx comes with a module plot_param that allows visualizing the fitting
results interactively.
Options
| Option | Description |
|---|---|
-p, --parameters | Specify the files containing the fitted parameters to be plotted |
-n, --parname | Specify the name of the parameter to plot |
Example
An example use of the module is given in the
protein-ligand binding example. After finish running
run.sh, the chemical shift differences between the free and bound states can
be displayed with:
chemex plot_param -p Output/STEP2/All/Parameters/fitted.toml -n DW_AB
and the transverse relaxation rates of both states can be compared with:
chemex plot_param -p Output/STEP2/All/Parameters/fitted.toml -n R2
These two commands are saved in the plot_param.sh script in
this example. From these two observables, the core
region of the interaction site can be clearly located. Aside from the core
region, there is also a tail with increased R2 rates located at
C-terminal end of the interaction site and with very little chemical shift
perturbation. This region is likely involved in the transient interactions with
the binding partner, which causes certain degree of steric restriction to this
region.
Getting initial estimates of Δϖ for CEST experiments
In CEST (and also D-CEST/COS-CEST) experiments, it is necessary to choose
suitable initial value of Δϖ to avoid getting trapped in a local minimum. ChemEx
comes with a module pick_cest for manually picking the major and minor dips of
CEST profiles, which correspond to the ground and excited states, respectively.
A typical command for such purpose is like this:
chemex pick_cest -e <FILE> -o <DIR>
After typing this command, a window showing all CEST profiles will appear. For
each profile first click on the major dip and then on the minor dip(s). Note
that in certain profiles only one dip could be visible, which indicates the
minor dip is overlapped with the major dip, therefore the major dip should be
clicked twice. When done with any profile, click the Next or Previous button
to proceed to the next or previous profile. The Swap button allows switching
between the major and minor states. The Clear button allows cleaning the
selection in the current profile. Two separate files will be created in
real-time during the dip picking process: cs_a.toml and dw_ab.toml that
contain chemical shifts of the major state and chemical shift difference between
the major and minor states, respectively.
Example
Try to run the pick_cest.sh script under
CEST_15N/ example
and pick_dcest.sh script under
DCEST_15N/ example
to learn how to make use of this function for CEST and D-CEST experiments,
respectively.