MoKa manual
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Chapter 4. MoKa graphical user interface (GUI)

MoKa is a desktop application for fast and accurate pKa prediction of organic compounds. This is what MoKa looks like:

Figure 4-1. MoKa Graphical Interface

Now that you have a visual map of the basic functions, here is a quick guide to what each of these elements does, by category, and how to use them.

4.1. The Menus

Here are the menus displayed on the MoKa menu bar (left to right), along with the commands in each menu.

File menu

Open - Opens an SD/mol2 file
Save sandbox as - Saves structures drawn in the sandbox as SD file. Please note that external SD files cannot be saved using this option
Exit - Quits MoKa

Tools menu

Rename from attribute... - Renames objects from attribute data (SD files only).
Sandbox
- New... - Opens the depiction tool to draw a new molecule.
- New from existing - Opens the depiction tool to edit the molecule currently displayed.
- Clone - Clones the structure currently depicted into the Sandbox
- Clear - Clears the Molecule view pane
Paste in sandbox - Pastes mol file from ISIS/Draw into the Sandbox.
Note: The Paste from ISIS/Draw button is available only in Windows
Batch calculation... - Opens a window for batch calculation options
Load custom model... - Opens a window to choose in your file system the .mdk file containing the custom model
Restore standard model - Restores the MoKa standard internal models

View menu

Show/hide tautomers window - Opens the tautomers window
Show log window - Opens the log window
Compute layout - Recomputes atoms coordinates in the Molecule view pane; when disabled, the original coordinates as read from the input file are used.
Annotate depiction with pKa values - Displays pKa values in the Molecule view pane
Save snapshot - Saves the content of the Molecule view pane as an image file (.png)

Help menu

Manual - Opens the manual
About - Displays the software version

4.2. Working with MoKa

This section describes how to navigate through the MoKa Graphical User Interface

4.2.1. Importing Your Data

Import your molecules from SD or mol2 files. MoKa provides support for SD and mol2 (or multi-mol2) files. Load your file and all the structure names appear in the left-hand pane. MoKa automatically retrieves the name of the structure from the first line at the beginning of the molecular structures. If this line is empty, MoKa identifies each structure by using consecutive identifiers (obj00001, obj00002, etc.).

Copy and Paste from ISIS/Draw. Import your structure from ISIS/Draw. Before you can copy and paste from ISIS/Draw you may first need to activate the Copy Mol/Rxn setting within the application. To do this, open ISIS/Draw, and make sure the box next to the Copy Mol/Rxn File is checked (Options > Settings and General).

Use the Sandbox to sketch your structure or to edit the current molecule. You can sketch a new molecule using the Sandbox. Upon opening the Sandbox, the depiction tool can be accessed (Tools > Sandbox > Add molecule).

As you scroll up and down your molecules, you may want to edit the current structure. The Sandbox allows you to open the depiction tool and sketch a molecule starting from the current structure. The molecule in the SandBox can be exported as an SD file. If you wish, you can clear the content of the Sandbox (Tools > Sandbox > Clear).

4.2.2. MoKa pKa predictions

Annotate your molecule with pKa values. View the predicted pKa values in the pKa values pane and select each pKa to display the corresponding ionizable site. The atom numbers of the ionizable sites are provided for each predicted pKa. You can check the accuracy of the predicted pKa using two parameters:

SD - Assuming that the structure given is well known to MoKa, the standard deviation of the model used for a prediction expresses the accuracy of the pKa.
QP - The quality parameter is a rough estimate of the error in log units. A QP = 0 indicates that the predicted pKa has the same accuracy of a compound included in the training set. Therefore, the substructure of that compound is known and the prediction is very reliable. A QP higher or lower than zero indicates that some fragments are unknown. The higher the absolute value of the QP, the higher is the expected effect of these fragments on the pKa value. The +/- sign before QP specifies whether the unknown fragment is expected to shift pKa upwards or downwards.

QP is aimed at understanding the level of accuracy of predicted pKa values. According to the technique used, error ranges are usually well known when performing experimental measurements. However, errors in predicted values are more difficult to estimate, because the prediction method used affects the size of the error, and the similarity of the predicted compounds to those in the training set is important.

4.2.3. Tautomers

Choose the most suitable tautomeric form for pKa calculation. Because tautomers correspond to distinct chemical species, the pKa value obtained experimentally is a result of the mixture of species found in solution. Since one single species is usually strongly favoured compared to all others, the experimentally measured pKa is the most close to the pKa of the preferred tautomeric form.

For each molecule being processed, MoKa checks quickly for potential tautomerism. If an unstable form is suspected, MoKa prompts you to Check tautomers. With the tautomer window opened (View->Show/hide tautomer window) click Generate. The tautomeric form expected to be the most stable in the aqueous medium will be displayed along with the newly predicted pKa values. You can copy the stable form to the sandbox by clicking on the button on the right side of the table.

If necessary, open the tab All tautomers to view other possible tautomeric forms.

4.2.4. The Graph

Use the species abundance graph to visualize the ionization pattern of your compound. This is an interactive graph that displays the structure in the ionization state predicted at the pH value selected. Each curve on the graph corresponds to an individual species, which is automatically displayed in the Molecule view pane. Click on the point of the curve of interest at the desired pH: MoKa calculates and shows the percentage of the corresponding species in aqueous solution.

4.2.5. Exporting Your Results: batch calculation and snapshot

Use the Batch calculation and export all your results to a plain text file. MoKa can export the results of a computation to a text file or to an SD file using the Batch calculation button. The following dialog box appears:

Before starting the batch calculation, make sure that you have chosen the required settings.

Choose input and output files. Input file can be in SD, mol2, or multi-mol2 format; output can be in plain text (use a filename with ".txt" extension) or SD (".sd" extension) format. The results are written according to an easily parsable output format.
If your input file is an SD file, you can assign the name from one of the attributes by typing the attribute tag in the Assign name from attribute (SD only) bar. By default MoKa retrieves the names of the molecules in the SD/mol2 line that marks the beginning of a new molecule. If this line is empty, names are replaced by consecutive identifiers (object0001, object00002...)
Check this box to activate tautomers correction over your batch calculation. If your input structure is unstable, MoKa computes the pKa of the stable form, therefore atom numbers of ionizable sites are subjected to change. If you are exporting to the SD file format the input unstable form is changed to the stable tautomer
Select the maximum number of acidic and basic pKas to output by using the Show predictions for pane. For example, when you only want one acidic pKa, select 1 acid center. Only the lowest pKa is exported when more than one acidic pKa is present. Similarly, in allowing for a maximum of n basic centers, only the stronger bases (higher pKa) are exported.
Optionally the output file can include additional data:
- the standard deviation (SD)
- the quality parameter (QP)
- the predicted LogP value
- the predicted LogD values at specified pH
QP and SD will be added to the main result line while LogP and LogD values will be added as new SD attributes. See format details in Section 5.1.
If you need to filter the pKa values, click the Filter options... button and the following dialog window appears:
Select the desired cutoff filters in the dialog box that appears. For example, if you need to display only acids with pKa lower than 7.0, you should use the following settings (for acids only):
- Upper limit: 7.00
- Lower limit: -10.00
You can also filter your results by QP value. Please remember that the default range -3.5...+3.5 should not be increased to higher values.

Capture a snapshot of the current molecule with the annotated pKa values. If you need to save your calculations and include a picture of the molecule used, you can capture a snapshot of the current molecule. You can embed the pKa values in the molecular structure by clicking on the Activate depiction with pKa values button.

4.2.6. Custom models

Extend the accuracy of pKa calculations by loading a custom model generated by Kibitzer. MoKa calculates pKa by using a set of built-in pKa prediction models. You can also load customized models generated by Kibitzer and built from your experimental pKa values. The custom models are based on MoKa internal models biased by your database of pKa values. Loading your custom model, stored in a .mkd file, automatically updates all the experimental pKa values accordingly (Tools->Load custom model...)

Note: It is possible to load a custom model at program startup by using the --load-model option, like this: moka --load-model=modelname

The bottom left bar in the MoKa main window displays the model you are currently using. If you wish to return to the standard model, then select: Tools->Restore standard model.

4.3. Technical info

Limitations.

MoKa only accounts for the following atoms: H, B, C, N, O, F, Si, P, S, Cl, As, Se, Br, Sn, and I. The effect that any other atom might have on the pKa is disregarded.
The current version of MoKa is not suitable to compute the pKa of folded proteins. If you import a peptide (mol2 and SD format only), the predicted pKa values correspond to the pKas of the open chain.
The MoKa internal database is not available for browsing.

Capabilities.

The presence of counter-ions does not affect the value of the predicted pKa
You can import multiple molecular structures as a single one. For example, you can import a molecule with its counter-ion (Cl^-, oxalate, etc.) or any other compound. Provided that there is no connectivity between two or more molecules, MoKa computes pKa by considering the structures as being independent.
MoKa accepts structures in neutral, protonated, and deprotonated form. The pKa of an ionizable site does not depend on its ionization state, so regardless of the species given, the predicted pKa remains the same.

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