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Epik Panel |
In the Epik panel you can set up and run a job that predicts the pKa of the ionizable atoms in your structures, or generates structures with probable ionization and tautomerization states based on the predicted pKa values.
To open the Epik panel, you can:
Choose Applications → Epik in the main window.
Choose Tasks → pKa Prediction → Empirical in the main window.
The tasks available from the Epik panel are the prediction of the pKa values of the ionizable atoms in a set of structures, either for independent or for successive protonation or deprotonation, and the generation of the probable ionized (and tautomerized) states of a set of structures within a given pH range. The pKa predictions are rule-based, and so can be generated very rapidly. The pKa values are stored as atomic properties with the structure, and can be used for the filtering of structures.
When the Epik job finishes, the pKa values are automatically displayed on the structures in the Workspace as atom labels. The labels can be cleared in the Atom Labels Panel. Uncertainties are provided with the pKa predictions.
Epik produces a number of properties that are listed in the Project Table. The most important of these are:
To predict independent pKa values for a set of structures:
Select the source of the structures using the tools at the top of the panel.
Select the Query only option for the Analysis mode.
Choose the solvent from the Solvent option menu.
Click Run.
To generate the ionization and tautomerization states of structures within a given pH range:
Select the source of the structures using the tools at the top of the panel.
Select the Predict states option for the Analysis mode.
Choose the solvent from the Solvent option menu.
Enter the target pH and range in the pH text boxes.
If you want to keep the original ionization state, regardless of its probability in the given pH range, select Include original ionization state.
If the structures tautomerize, either in the original or the ionized state, select Generate tautomers. To keep the original tautomer, regardless of its probability in the given pH range, select Include original tautomer.
If you are interested in structures bound to a metal in a protein, select Add metal-binding states.
Enter the maximum number of structures to generate for each input structure in the Maximum number of output structures text box.
Click Run.
To predict sequential pKa values for a set of structures:
Select the source of the structures using the tools at the top of the panel.
Select the Sequential pKa option for the Analysis mode.
Choose the solvent from the Solvent option menu.
Enter the target pH in the pH text box.
Click Run.
If you have a large number of structures, you might want to make job settings to select a host and distribute the job over multiple processors before starting the job. To do so, choose Job Settings from the Settings button menu
and make the settings in the Job Settings dialog box. Then click Run to run the job.
Choose the source of the structures for the current task.
If you chose File from the Use structures from option menu, enter the file name in this text box, or click Browse and navigate to the structure file. The name of the file you selected is displayed in the text box.
Select the source of structures from the Use structures from option menu. If the structure source is a file, enter the file name in the File text box, or click Browse, and navigate to the input file in the file selector that is displayed.
Query only: Predict pKa values of the input structures without doing any structural variation.
Predict states: Generate most probable states within a supplied pH range, and return structures as well as pKa values.
Sequential pKa values: Predict pKa values for successive protonation or deprotonation of the molecule. The pKa values are adjusted after the addition or removal of each proton.
Choose the solvent for the pKa predictions. The pKa values are stored for each solvent. The choices are H2O and DMSO.
Specify the target pH value and the amount of variation from this value inside which the generated ionization states can have a significant population.
When generating ionized output structures, keep the original ionization state, regardless of its relative probability in the given pH range.
Enter the file name of a custom pKa parameter file, or click Browse and navigate to the file. See the pKa Data File Format appendix in the Epik User Manual for more information.
Generate tautomers option: If selected, generate tautomers of the original and ionized structure.
Include original tautomer option: If Generate tautomers is selected, this option ensures the inclusion of the original tautomeric state, regardless of its relative probability in the given pH range.
Enter the file name of a custom tautomer parameter file, or click Browse and navigate to the file. See the Tautomer Database Format appendix in the Epik User Manual for more information.
Generate states appropriate for binding to metals in a protein, in addition to those for solution. With this option selected, Epik explores the removal of additional protons from heavy atoms that could potentially bind to metal atoms in the binding site of a protein.
Enter the file name of a custom metal binding parameter file, or click Browse and navigate to the file.
Enter the maximum number of structures to be generated for each input structure in this text box. If the number of structures with significant probability in the given pH range is greater than this number, return the most probable structures.
The Job toolbar is used to make settings for a job and to start it.
Enter a name for the job in this text box.
This button opens the Job Settings dialog box. The arrow to the right opens a menu, from which you can make settings or perform actions that are related to the job.
The menu items are described below.
This icon indicates when there are jobs running for the application that belong to the current project. It starts spinning when the first job starts, and stops when there are no more jobs running. If a job fails to start, it changes to an exclamation point.
Clicking the button shows a small job status window that lists the job name and status for all active jobs submitted from the current panel (for Jaguar and MacroModel this means all jobs from any of the application panels). You can double-click on a row to open the Monitor panel and monitor the job, or click the Monitor button to open the Monitor panel and close the job status window. The job status is updated while the window is open. If a job finishes while the window is open, the job remains displayed but with the new status. The rows are colored according to the status: yellow for submitted, green for launched, running, or finished, red for incorporated, died, or killed. Click anywhere outside the window to close it.
Run the job with the current job settings.
The status bar displays information about the current job settings for the panel. This includes the job name, task name and task settings (if any), number of subjobs (if any) and the host name and job incorporation setting. It also displays a message for a short time when you start a new job.
The status bar also contains the Help button, which opens the help topic for the panel.
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