1. Scientific & technical presentation Calculator Plugins József Szegezdi, Nóra Máté Sept 2005

2. Calculator Plugin Features Key features: Plugin modules are packed in dynamically loadable JARs. Extendible plugin set. API support: plugin class loading and instantiation plugin handling (parameter and input setting, running, getting results) GUI access (parameter and result display panels) Built-in access from multiple platforms: Marvin GUI (msketch, mview applications and applets) cxcalc command line tool Chemical Terms: evaluate command line tool search filtering JChem cartridge reaction processing

3. Calculator Plugins Available Calculations Elemental analysis Charge distribution Polarizability pK a logP logD Polar surface area Huckel Analysis H-bond donor-acceptor Major microspecies Refractivity Tautomer Resonance Isoeletric point Calculation Interface Marvin GUI Command line Chemical Terms API

4. Marvin GUI – menu Plugins are listed in the Tools menu. Plugin configuration is read from the xjars/plugins.properties property file.

5. Marvin GUI – parameter panels Parameter panels are usually created from XML configuration. In this way it is possible to set plugin parameters before the plugin JAR is loaded, which can be important in case of applets. These XMLs are stored under the xjars directory with file names: Parameters.xml

6. Marvin GUI – result display molecular results are stored in molecule properties atomic results are stored in atom labels Calculation results are displayed based on the decorated result molecule provided by the plugin: Custom result display (e.g. a chart) can also be provided.

7. Command line access: cxcalc Plugin calculations can be run by the command line tool cxcalc. The plugin configuration is read from xjars/calc.properties. All calculations are listed in the help text: Calculation specific help is also available: pKa (strongest acidic and basic pKa values) and major microspecies (pH=7.4) calculation:

8. Chemical Terms Chemical expressions can refer to plugins by calculation IDs specified in the XML configuration. The built-in configuration is described in http://www.jchem.com/doc/user/EvaluatorTables.html Examples: basic pKa value on atom 5 (0-based): evaluate –e bpka(5) test.mrv true if partial charge on atom 5 is greater than on atom 0: evaluate –e charge(5) > charge(0) test.mrv bromination - select aromatic carbon with minimal energy: react –r [c:1][H:2]>>[c:1][Br:3]..s:-energyE(ratom(1)) Nc1ccccc1 perform search on targets with mol mass greater than 150: jcsearch –e mass() > 150 –q query.mrv targets.mrv accept only search hits with acidic pKa less than 5 on target atom matching query atom with map 1: jcsearch –e apka(hm(1)) < 5 –q query.mrv targets.mrv

9. Plugin Handling – API without GUI 1.Create the plugin object: for built-in plugins in applications the plugin class is available in the application JAR (MarvinBeans.jar, jchem.jar), therefore you can simply use the plugin constructor for custom plugins or in case of applets the plugin classes should be loaded from the plugin JAR; use CalculatorPlugin.create(String clname, String jar) 2.Set plugin parameters by plugin specific API 3.Set the input molecule by CalculatorPlugin.setMolecule(Molecule) 4.Run the calculation by CalculatorPlugin.run() 5.Get calculation results by plugin specific API API usage examples are written in the apidoc class headers. Links: http://www.chemaxon.com/marvin/doc/dev/plugins.html#examples

10. Plugin Handling – GUI access from API PluginFactory xjars/plugins.propertiesjava.util.Properties object CalculatorPlugin subclass instance parameter panel as ParameterPanelHandler CalculatorPluginDisplay object or subclass instance XML JAR JAR or default or

11. Custom Plugin Application This custom plugin application shows: custom plugin implementation and configuration test application with customized GUI access

12. Custom Plugin Implementation – the plugin class I. The plugin class extends CalculatorPlugin: The setParameters() method will be called with parameters set in the graphical parameter panel by the user:

13. Custom Plugin Implementation – the plugin class II. The setInputMolecule() method will be called to set the molecule drawn in the sketcher: The run() method performs the main calculation:

14. Custom Plugin Implementation – the plugin class III. The getResultMolecule() method will be called by the default CalculatorPluginDisplay to display the molecule in a viewer, with molecular results in text labels and atomic results in atom labels: molecular results should be stored in molecule properties set by Molecule.setProperty() atomic results should be stored in atom labels set by MolAtom.setExtraLabel()

15. Custom Plugin Implementation – the plugin class IV. Standardization: most calculations require input molecules being in standardized form. The default standardization aromatizes the molecule and converts nitro and sulphynil groups: To customize standardization, overwrite the standardize() method. In our SelectionPlugin we do not need standardization at all, therefore we implement standardize() with an empty body:

16. Custom Plugin Implementation – the display class I. The display class is responsible for showing plugin results in a graphical component. The default display is CalculatorPluginDisplay, it calls CalculatorPlugin.getResultMolecule() to show the calculation results in a decorated Molecule. This result molecule stores the computed chemical features in molecule properties (Molecule.setProperty()) and atom labels (MolAtom.setExtraLabel()). To customize the display, extend the CalculatorPluginDisplay class:

17. Custom Plugin Implementation – the display class II. The graphical component displaying the calculation results is returned in getResultComponent(): You can insert the default decorated molecule viewer into the custom display by calling CalculatorPluginDisplay.createViewPanel(). You can fetch display parameters set in the graphical parameter panel by implementing setParameters():

18. Custom Plugin Implementation – the display class III. Error handling: CalculatorPluginDisplay shows error and warning messages returned by CalculatorPlugin.getErrorMessage() and CalculatorPlugin.getWarningMessage() in case when CalculatorPlugin.run() returns false. To customize error display, implement getErrorComponent(): Parameter panel: PluginFactory can create generic parameter panels from XML configuration. However, if you need a parameter panel that is not supported by this framework, return your parameter panel in getParameterPanel():

19. Custom Plugin Implementation – parameter panel Parameter panel: PluginFactory can create generic parameter panels from XML configuration: xjars/ Parameters.xml Our parameter panel configuration file is SelectionPluginParameters.xml:

20. To access our plugin from the Marvin Tools menu, we have to accomplish the following steps: 1.Create the plugin JAR with manifest SelectionPlugin.txt: The manifest can also refer to additional JARs in its Class-Path attribute. The manifest file can be omitted if the plugin name is specified in the configuration (e.g. xjars/plugins.properties, xjars/calc.properties) and no other resources are needed to load the plugin. 2.Copy the plugin JAR and the parameter XML into the xjars directory. Custom Plugin Implementation – administration I.

21. Custom Plugin Implementation – administration II. 3.Insert a line into xjars/plugins.properties: SelectionPlugin access is added to your Tools menu in the viewer and the sketcher applets / applications.

22. Custom Plugin Implementation – custom application I. The following test application shows a customized way to access our plugin. Two buttons are placed to show the OptionsPane (plugin specific parameter panel with OK, Cancel and Display buttons) and to run the plugin. Configuration is given to PluginFactory in a java.util.Properties object.

23. Custom Plugin Implementation – custom application II. Create PluginFactory, set our class as Display button ActionListener and parent component of OptionsPane, set plugin configuration in factory.

24. Custom Plugin Implementation – custom application III. Event handling: Show OptionsPane if the Set parameters button is pressed. Run plugin if the Run plugin button is pressed. Run plugin if the Display button is pressed on the OptionsPane. Note, that the action command is set to plugin_.

25. Custom Plugin Implementation – custom application IV. Show the OptionsPane: 1.Get the plugin index from the factory. 2.Get and show the plugin OptionsPane.

26. Custom Plugin Implementation – custom application V. Run the plugin: 1.Get the plugin index. 2.Get the plugin. 3.Get the display. 4.Get plugin parameters from the OptionsPane. 5.Handle license key. 6.Set parameters in plugin and display.

27. Custom Plugin Implementation – custom application VI. 7.Check input molecule. 8.Set molecule. 9.Run the plugin. 10.Store results in display. 11.Get result component. 12.Show result component.

28. Custom Plugin Implementation – references The SelectionPlugin example code will be available in the next Marvin release: Marvin 4.0. You will find it under the directory examples/plugin See its index.html for installation instructions.

29. Elemental Analysis

30. Polar Surface Area

31. Partial Charge Distribution

32. Partial Charge Distribution Calculation Partial Equalization of Orbital Electronegativities (PEOE) Orbital electronegativity defined by Mulliken Orbital electronegativity of atom i: i =a t +b t q i +c t q i 2 q i : partial charge Partial charge of atom i is iteratively calculated based on Gasteigers method: i (0) = a t q i (0) = 0 q i (n+1) = q i (n) + ) n ( i - k )/ max( i, k ) k: index of a neighbor of atom i

33. Polarizability

34. logP

35. logP = f i f I : atomic logP increment logP Example

36. Validation of the logP prediction

37. logD

38. logD is computed using micro ionization constants (k i ), micro partition coefficients (p i ), and pH 123 (0) 1 + (1) 2 + (2) 3 - (3) 1 + 2 + (4 ) 1 + 3 - (5) 2 + 3 - (6) 1 + 2 + 3 - (7) k1k1 k2k2 k3k3 k4k4 k5k5 k6k6 k7k7 logD Example 1 2 3

39. pKapKa

40. The large model of the pK a calculation The large model is invoked when the number of the ionizable atoms in the molecule is larger than 8 The macro distribution of the molecule as the function of pH also calculated beside the pK a values

41. pK a Plugin - Microconstants Micro ionization constants (logk) are calculated from regression equations that have three types of calculated parameters: Polarizabilities Partial charges Intramolecular interactions logk

42. Macro ionization constants (pK a ) are calculated from the microconstants (logk) pK a Plugin - Macroconstants Ionization scheme 1 - 1 - 2 + 1232 + 1 - 3 - 1 - 2 + 3 - 3 - 2 + 3 -

43. Hydrogen Bonds in pK a Calculation hydrogen bond

44. Validation of the pK a prediction

45. Tautomerisation Plugin Tautomer structures are generated for any molecule

46. Resonance Plugin

47. Isoelectric Point Plugin

48. Visit other technical presentations MarvinSketch/View http://www.chemaxon.com/MarvinSketch_View.ppt http://www.chemaxon.com/MarvinSketch_View.ppt MarvinSpace http://www.chemaxon.com/MarvinSpace.ppt http://www.chemaxon.com/MarvinSpace.ppt Calculator Plugins http://www.chemaxon.com/Calculator_Plugins.ppt http://www.chemaxon.com/Calculator_Plugins.ppt JChem Base http://www.chemaxon.com/JChem_Base.ppt http://www.chemaxon.com/JChem_Base.ppt JChem Cartridge http://www.chemaxon.com/JChem_Cartridge.ppt http://www.chemaxon.com/JChem_Cartridge.ppt Standardizer http://www.chemaxon.com/Standardizer.ppt http://www.chemaxon.com/Standardizer.ppt Screen http://www.chemaxon.com/Screen.ppt http://www.chemaxon.com/Screen.ppt JKlustor http://www.chemaxon.com/JKlustor.ppt http://www.chemaxon.com/JKlustor.ppt Fragmenter http://www.chemaxon.com/Fragmenter.ppt http://www.chemaxon.com/Fragmenter.ppt Reactor http://www.chemaxon.com/Reactor.ppt http://www.chemaxon.com/Reactor.ppt

49. References Built-in plugin descriptions: http://www.chemaxon.com/marvin/chemaxon/marvin/help/calculator-plugins.html Developers guide with API usage examples: http://www.chemaxon.com/marvin/doc/dev/plugins.html Plugin framework API (chemaxon.marvin.plugin) (subject to major changes in Marvin 4.0): http://www.chemaxon.com/marvin/doc/api/chemaxon/marvin/plugin/package-summary.html Built-in plugins API (chemaxon.marvin.calculations): http://www.chemaxon.com/marvin/doc/api/chemaxon/marvin/calculations/package-summary.html