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Chapter 46. Greater
Greater is a Graphical User Interface (GUI) for the GRID package of Programmes. It provides GUI access to most of the functionality of Programmes GRIN and GRID and also to Programme GREAT which was the predecessor of Greater. Furthermore the interactive Graphical User Interface of Greater is closely integrated with GVIEW, and this helps the user to visualise the structure of the Target and the results of the GRID computation simultaneously.
In fact Greater is a sophisticated "wrapper" for the suite of GRID Programmes, and it works in two integrated stages. First the necessary command files are produced for GRIN and/or GRID, and then the Programmes are started and run in the correct sequence. Thus a job under the control of Greater uses exactly the same programmes and data as an experienced User would use when setting up the jobs manually, and the Programmes are at all times directly accessible in command mode. The whole process under Greater is fully transparent to the User who can import target structures, compute the Molecular Interaction Fields (MIFs) and view or export the results within the interactive graphical interface.
Greater was designed to suit the needs of both beginners and advanced Users, but the GRID package contains many functionalities and some of these are not supported by the current version of Greater. When Users require access to some of the more advanced functionalities, directives and options they may still have to use the traditional command-mode interface.
Credits
Greater was written by Manuel Pastor, Grup de Recerca en Informātica Biomčdica (GRIB) at IMIM/UPF, Barcelona, Spain in the framework of a collaboration project with Molecular Discovery Ltd. Support for Greater can be obtained directly from Molecular Discovery Ltd.
46.1. Installation and configuration
Greater is automatically installed together with the other Programmes when the GRID software package is installed on a processor. Then, when Greater is first used, it needs to know the path to the main GRID executables, and to GRIN, GRID and GVIEW in particular. If the environment variable GRID_DIR has been set, Greater will use this variable. If not, it will prompt the User to define the path where the GRID package has been installed, and the name of the grub.dat datafile which should be used.
Configuration options are normally written to a file called .greaterc, in the root directory of the User. However, if you want to make Greater available system-wide, the best way is to set up the GRID_DIR variable in the system shell resource file. The appropriate setting depends on the operating system and the shell which has been defined for Users. Here are some examples:
| OS | shell | action |
| IRIX | csh or tcsh | In the file /etc/cshrc add the line: setenv GRID_DIR /usr/local/grid |
| LINUX | csh or tcsh | In the file /etc/csh.cshrc add the line: setenv GRID_DIR /usr/local/grid |
| LINUX | bash | In the file /etc/bashrc add the line: GRID_DIR="/usr/local/grid" export GRID_DIR |
Greater needs to use a number of graphic libraries that are present in the distribution directory. Therefore, the environment variable LD_LIBRARY_PATH (or LD_LIBRARYN32_PATH in IRIX 6.5) should include the GRID install directory. Please consult Chapter 2 for further information.
To start a new run with Greater in a UNIX shell type:
Greater
If you want to use Greater to load a pre-saved computation type
Greater filename.grib
where filename.grib is the name of the Greater computation previously saved.
46.1.1. Options
There are several options available to the User in order to customise the default Greater behaviour. The following dialog is shown selecting File->Set options...
In the first tab (General) the User can set the path to the GRID installation directory and to the grub.dat file. Moreover, unchecking the "splash" option the splash screen shown at Greater startup will be disabled; the housekeeping option controls if Greater should keep every file produced by Grid (default setting), "remove backup" files (*.1, *.2 and so on) or "also remove LOUT/LONT" files.
The "Text viewers and editors" tab is used to change the "Fixed font" used to visualise text files and the default colors for warning (default: yellow) and error (default: red) messages.
The "PDB filtering" tab is used the default filtering level used by Greater. With the "GRIN LEVL keyword" option, the User controls the amount of additional information printed in GRIDLONT files. The bigger is the value, the more verbose will be the information printed in GRIDLONT. An advanced explanation of the filtering options is available here.
In the "GRIN keywords" tab the User can set default options passed to the Grin programme.
ALMD controls the printing of extra information in the GRIDKONT file.
MOVE controls the flexibility of the target. We strongly recommend to leave this directive in it's default value (1).
IHVA determines whether Lennard-Jones variables and electrostatic charges will be assigned to the hydrogen-bonding hydrogen atoms which are bonded to ATOMS. More information can be found in Section 20.2.
When the IHAC directive is set to 1, GRIN will compute atomic charges using a semi-empirical quantum chemical calculation. More details can be found in the GRIN manual.
46.2. Importing target structures into Greater
The starting point of any GRID computation is importing the structure of one or more target molecules, and the structure of the target must be provided in a 3D format which is supported by Greater. At present, the supported external formats are:
| Type | Default ext. | Description |
| PDB | .pdb | Brookhaven PDB format is suitable for proteins and other biomolecules. The standard PDB format recommendations should be followed, and GRIN will issue warning messages about faulty PDB files. |
| mol2 | .mol2 | mol2 format which is most suitable for small molecules. A single mol2 file can contain many structures, and in this case it is called a MultiMol2 file. The atom types assigned in a mol2 file are not used for assigning GRID atom types, but the bond order and the 3D geometry of the molecule is critically important. |
| SDFile | .sdf | SDFiles are highly suitable when a series of small molecules is to be studied. The file must contain suitable 3D coordinates for the atoms, and should include the hydrogens. SDFiles describing only the 2D structure of the molecules are not acceptable for direct use by GRID. As with .mol2 files, the bond order and the 3D geometry of the compounds is critically important. |
Greater also supports the KOUT format produced by Programme GRIN.
The method of inputting Target structures to Greater depends on the number of structures which are to be studied.
46.2.1. Single target
If you want to work with a single target, use the command Targets->Add single target or press the button Add single in the toolbar. Either option opens a dialog window like this:
In this dialog window you can:
Select the format of the input file (PDB, mol2, SDFile or kout). Alternatively, if you work in auto mode (the default), then Greater will guess the format from the file extension.
Enter the name of the input file. You can either type the file name, or press the "..." button to open a standard file browser.
Select the filtering level. (This filter has no effect for file formats other than PDB).
Once the file name has been entered and you have pressed the OK button, Greater will use Programme GRIN to convert your input format into the internal KOUT format used by Programme GRID. It does this as a background job, and the message "ready" will appear if the conversion to KOUT format was successful.
46.2.2. Multiple targets
Many Targets can be imported by Greater for sequential processing in a batch job. You can either import the individual targets one by one, using the method described above until the whole batch is ready, or you can introduce the whole batch simultaneously. A third approach is to import a single file which describes many structures (i.e: a MultiMol2 or SDFile) or, finally, Greater can read a list of files which will then be imported sequentially. All these methods can be accessed by using the command Targets->Add Multiple targets... or by pressing the button Add multiple on the toolbar. In either case the following dialog window will be shown.
46.2.2.1. List file
Using this tab you can import a set of files listed in a plain text file. Enter the filename in the List file field or use the ... button on the right to open a standard file browser.
46.2.2.2. File set
Type directly the names of the files in the "Files to import" text area (You can enter as many file names as you wish). You can also use the copy and paste abilities of your desktop to add file names, such as those produced by the command: ls -1 in a standard Unix shell. Alternatively, you can press the button: "Add listfile" and dump the contents of a plain text file into the import window (This text file would, of course, contain a list of the names of the files which were needed in the import window). Greater does not require any particular format for this list, but the recommended format is to write the correct name for each file on a separate line. Blank lines and spaces will be ignored. The programme will recognise the file format from the extension, which must be one of those specified above.
Select the Filtering level. (This filter has no effect for file formats other than PDB).
Once you have pressed the OK button, Greater will use Programme GRIN to convert each of these individual filtered files into the internal KOUT format used by GRID. It does this as a background job, and several new lines will appear followed by the message "ready" if the conversion has been successful.
You can press the button Clean to empty the import window and start again.
46.2.2.3. Multi-mol file
Enter the name of the file. You can type the file name or press the "..." button on the right to open a standard file browser.
Select the format of the file (SDFile or MultiMol2). Alternatively, if you work in auto mode (the default), then Greater will guess the format from the file extension.
Once you have pressed the OK button, Greater will split the multi-structure file into the appropriate number of single structure files which will be named: sdf00000.sdf, sdf00001.sdf, etc.... Greater will then use Programme GRIN to convert each of these individual files into the internal KOUT format used by GRID. It does this as a background job, and several new lines will appear followed by the message "ready" if the conversion has been successful.
46.2.3. Aborting an import
The import of large sets of compounds can be time-consuming. GRIN runs can be stopped from Greater by using the command: Targets->Abort import or clicking the red Abort button in the toolbar. Computations in process are stopped without waiting for the associated programs to finish the current task, and the output files may therefore be incomplete.
46.2.4. Managing targets
Imported Targets are shown in the Target window of the Greater interface, each on a separate line. The information for each Target shows:
- Molecule name.
This is an editable field and can be changed to assign a more informative Target name.
- Status.
This field shows whether the all the preparative work for each Target has been done correctly. If a Target has not been imported correctly its status line may be coloured yellow (GRIN warnings) or red (GRIN errors).
- Charge.
This is the total charge of each Target as computed by GRIN. By checking this charge the user may sometimes detect errors in a Target in a simple, quick, and practical way.
- Activity.
Every Target molecule can be associated to a certain numerical value, which will normally measure some biological property of the Target. When present, this value will be included with the final results of the computation, and may be exported to other applications. Activities can be entered editing this field. Alternatively activities can be imported from a plain text file reporting one activity value in a separate line for each target, using the command Field->Import activity list.
- Filename.
This is the name of the file defining the structure of the Target.
The User can select structures in the Target window by clicking on them with the mouse. To select more than one structure, keep the <SHIFT> key pressed and simultaneously hit the first one and the last. If these are non-consecutive keep the <CONTROL> key pressed, and hit on individual lines to change their selection status.
The interface provides a contextual menu that appears when the user presses the right hand mouse button. The options in this menu apply to the selected structures (whenever possible) like this:
- remove.
The selected target is removed from the list.
- view text files.
This commands shows a dialog window where different output files produced by GRIN and GRID, for all selected structures, are shown. This dialog is further described in the following section "Handling import errors".
- view structures.
This command uses GVIEW to show a 3D interactive representation of the first selected target structure.
- view fields.
This command uses GVIEW to show a 3D interactive representation of the first selected target structure, together with a computed field. Please note that this option can not be selected until the field has been computed. In some situations, when the fields are computed for all targets simultaneously, the program may only show the first molecule in the target list. However, when this happens the User can still change to another structure by pressing the <PgUp> and <PgDn> keys.
- reimport.
This command restarts the importing process for all the Targets which were not imported correctly.
- accept all errors.
This command overrides the safety checks which are built into Greater. It can be used to alter the status of a Target from 'warning' or 'error' to 'ready'. This should only be done after careful inspection of the Target files, and at the User's own risk.
Similar commands are present in the Target menu, but in this case, they are applied by default to the first Target in the list (View text files, View structure, View fields), or to all the Targets in the list (Reimport all Targets and Accept all errors), as appropriate. The button 'View' in the toolbar is equivalent to the command: Targets->View fields .
46.2.5. Handling import errors
Greater may sometimes not import a Target, and this may be due to various different reasons. The recommended procedure for dealing with this depends on whether it happens with a small compound imported in mol2 or SDFile format, or in a biomolecule imported as a PDB file:
46.2.5.1. Small compounds
Greater uses an expert system to assign appropriate atom types to the individual atoms of each small molecule. For a correct assignment, the original mol2 or SDFile should contain correct bond orders, and an approximately correct 3D geometry. This means, for example, that aromatic rings should be very nearly flat! The accuracy of the atom type assignment by Greater will only depend on these two factors, and other information such as SYBYL atom types will be ignored.
The required atom types for GRIN and GRID will be written to a new PDB file with the same name as the original file, but with the extension changed to .pdb. If your PDB file has an unexpected atom charge, or if you get GRIN errors or GRIN warnings, you should select the relevant compound and inspect its PDB file using the command: view text file. Then inspect the molecule's structure using the command: view structure. It will often be found that the PDB file contains an unexpected assignment due either to an error in the bond order as shown in the original .mol2 file, or to a missing atom (Hydrogens are most frequently missing). Once this problem has been detected, you can correct the original mol2 or SDFile and reimport it to Greater.
46.2.5.2. Biomolecules
Many files in PDB format contain small syntactical mistakes, missing atoms, errors in the nomenclature of the atom types, etc... Programme GRIN thoroughly analyses each PDB file, and issues a warning for each mistake. These warnings can be visualised in Greater by selecting the command "View text files" and then selecting the GRINLOUT tab. The warnings and errors are highlighted in the colours defined in the preferences. In order to know the position of these residues and atoms, when the button "Plot conflicts" is pressed Greater will show a graphic representation of the Target molecule with the position of each error highlighted by a cross of the corresponding highlight or error colour.
PDB files can be edited within this dialog in Greater, because the viewer used for the PDB files has some editing capabilities, and the button Save allows the edited file to be resaved.
46.3. Neutralise targets
It often happens that newly imported targets show a net or fractional charge; for example:
this is due to a lack, in the PDB file, of a correct number of counter-ions to balance acid or basic moieties.
The following dialog is shown selecting Targets->Neutralise... from the menu:
and can be used to automatically neutralise macromolecular targets. The added counter-ions can be fixed to the computed position, or they can move from such positions when a probe is colliding with them. Check the "movable ions" option to activate flexible counter-ions.
In the "MINIM options" section, the User can define the "energy cut-off" parameter, a threshold value used by MINIM (more details about MINIM in Section 44.19)
The "interpolate" option allows interpolation of energy maps in order to obtain a better estimation of the counter-ions position. Please note that the total number of counter-ions added is automatically computed by Greater.
46.3.1. Add ions or water...
An interface to the programme Filmap (more information about Filmap in Section 44.3) is now available in Greater, selecting Targets->Add ions or water... from the menu:
This function is used to add water molecules or counter-ions any macromolecular target. The number of water molecules or ions to be added is selected by the User.
In the "MINIM options" section, the User can define the "energy cut-off" parameter, a threshold value used by MINIM (more details about MINIM in Section 44.19.
The "interpolate" option allows interpolation of energy maps in order to obtain a better estimation of the counter-ions position.
46.4. Defining a GRID computation
In order to set up a GRID run one must:
Select a chemical Probe. This is the chemical group whose interaction with the target will be simulated. It can be chosen from a menu in Greater, or can be defined by entering appropriate energy parameters.
Define parameters for the computation. Greater will provide sensible default parameters, but most Users will want to change some of these.
Define the position and size of the region in which the computation will be carried out. This region is called the Grid Box or Cage.
Greater provides a GUI for performing these three tasks. Here we describe this interface, but in order to fully understand these options and having a qualified opinion, the User is strongly encouraged to read the GRID manual.
46.4.1. Selecting probes
To choose a Probe one should select the command: Probes->Choose probes... or press the button Probes on the toolbar, or click on the Probes window. A dialog window will appear where the User can select a Probe or Probes to be used in the computation. The dialog has three tabs which represent the three categories of Probe: single-atom (eg: a carbonyl oxygen atom), multi-atom (eg: a carboxyl group), and special probes.
GRID allows one to carry out computations using several different single-atom Probes on a set of Targets, and so several single atom Probes can be selected in this dialog by simply clicking on their names. However, multi-atom Probes require more complex computations, and only one multi-atom Probe may be used in each Grid run. To choose this one click on the corresponding line of the dialogue box, remembering that not more than one selection is allowed.
The tab labelled special contains a list of probes recently introduced in the Grid executable.
>It is also possible to define a single-atom Probe by specifying its parameters (eg: Van der Waals radius, charge, etc). This is done by selecting the command: Probes->Define new probes.
Once the OK button has been pressed, the selected Probe or Probes are shown in the Probes window.
The dialog, by default, has the option "use probe symbols" checked, meaning that the Probes will be selected from the Probes list as described above. If you want to define your own Probe by specifying its energy parameters, start by deselecting this option. The exact meaning of these parameters is described in detail in the GRID manual, and you can enter the values which you want.
Press OK when you are satisfied with the settings, and the Probes window will show "CUSTOM" which means that the Probe for your computation will not be defined by a symbol but by the parameters which you have specified.
If you change your mind, and want to select a Probe from the Probes list after all, you can of course reselect the default option "use probe symbols".
46.4.2. Defining GRID directives
GRID directives (or keywords) used for the computation are shown in the window at the right-hand bottom corner. They have been grouped into four categories:
- The box.
This defines some characteristics of the grid cage which will be used for the computation, like the clearance in Angstrom by which the Grid extends beyond the target, or the number of planes per Angstrom which determines the resolution of the computation.
- The force field.
This defines the parameters describing how the computation will be carried out.
- The output.
This defines how the results of the computations will be written to the output files GRIDLONT and GRIDKONT.
- Advanced.
This may be used to define some miscellaneous advanced features.
Click on any of these categories to expand them, and see the names of the explicit directives together with their default values. Click on any individual directive to change its value, and you will see a dialog like this:
You can obtain the same dialog directly from the menu by selecting the command: Method->Change keywords. In this dialog you can see and change the value of the individual directives; restore the default values by pressing the default button; and see a concise description of each directive. (This concise description is just a brief reminder, and is not intended to replace the more detailed descriptions which can be found in Chapter 28).
You can "navigate" through the whole directive tree from this dialogue by pressing the 'Prev' and 'Next' Buttons. If you only want to alter one value you should make your change and press the OK button to close the dialog, and the altered value will then appear written in red. If you want to change several values, press the Apply button after each change, and this will leave the dialogue box open until you finally press OK.
46.4.3. Express setup
For a faster editing of the most common parameters, select Method->Express setup (CTRL-E) and the following window will let you define NPLA, LEAU, MOVE, NETA and ALMD directives:
46.4.4. Defining the box size
For small Targets, it is not usual to explicitly define the box in which the computation takes place. GRID will then compute the coordinates of a box large enough to accommodate all the atoms of the Target with an appropriate margin of clearance all round. (The size of this margin is defined by the directive CLER). However the User may only be interested only in a small region of the Target when a large biomolecule is being studied, such as an enzyme with an active cleft. In this case, the dimensions and position of the box for computation should be defined explicitly by using the command Method->Define box size...
When you start using this command you will find that the option "automatic" has been checked by default, meaning that GRID will define the box on its own. It will choose a box round the whole Target, and if you want to define your own smaller box you must start by deselecting the "automatic" option. The box size and position can then be entered by defining its most extreme X, Y and Z Cartesian coordinates, as defined in the GRID manual (eg: The coordinates of the top back right and the bottom front left corners of the box).
As an alternative, and only for biomolecules in kout or PDB format, Greater offers the option of defining the box by annotating a list of the protein's amino-acid residues. This list is only displayed for kout or PDB files, and the user simply selects a residue by double-clicking in its name and number. The box will then be created with an appropriate clearance around the chosen residue, and you can then visualise it in GVIEW and further modify its size and position by clicking the Interactive button. The following picture is a sample of this feature:
In this interactive graphic of the Target a box will be displayed, with an interactive manipulator and a handle at each corner and each face of the box. You just select the handlers in pick mode to change the dimensions of the box, or drag the whole box by picking a face and moving it to a different part of the Target. Your movements are automatically reflected in the values of the box corners, and when you are sure that the box is correct just press OK. Later, if you change your mind and want GRID to define the box after all, you can just click "automatic" again.
46.5. Running a GRID computation
The Compute->Run command is inactive until all the requisites for running the computation have been acceptably defined. In particular at least one Probe must have been selected, and at least one Target structure must have been imported and must be in the "ready" status. We most strongly recommend you to correct any GRIN warnings or GRIN errors, although it is possible to click the "accept errors" button and do your computation on a faulty Target!
The particular controls which are active or inactive at any moment depend on the context, and this should prevent the User from making inappropriate choices. The options in this dialog are important for defining the way in which GRID will produce its output, and to understand them you must be aware that GRID treats a single Target and a set of Targets quite differently. The detailed differences are defined by directive LIST, which is carefully described in the GRID manual.
The command shows this dialog:
In the tab labelled "Standard" three self explaining options are provided, defining the use of the MIF computed by Grid. The "visualise fields" option must be selected when the User needs to inspect graphically (that is, with GVIEW or other similar tools) the result of computation.
"export GRIDKONT" must be selected when GRID is used in tandem with other software or in other procedures like GOLPE, VOLSURF, COMBINE, ALMOND. This option produces a file in binary format.
"obtain readable GRIDKONT" is used to produce a human readable ouput file in standard ASCII format.
The next figure shows the "Advanced" tab, where the User can find the same options as in the "Standard" one, but labelled like in previous Greater versions.
46.5.1. Advanced details on LIST directive and GRIDKONT files
46.5.1.1. When studying a single target
When a single Target is being studied by itself, Greater normally runs GRID by defining the explicit GRINKOUT filename in the command file, and the GRID run then produces a single GRIDKONT output file. In this case only one Probe may be used, and the output will be written in binary code by default. This binary output is always produced for a single Target irrespective of the value of directive LIST, and is immediately ready for use as input to other Programmes. However, it is not readable by eye.
It is necessary to use directive LIST which is described in more detail below, if you actually want to read the output file by eye, but this cannot be done in a GRID run on one single Target. However, it is possible to trick GRID, so that it behaves as if it is studying a batch of several input files, and LIST may be used when this is done. This trick is to use a file list containing the name of just one Target file, instead of explicitly defining the filename of the Target. GRID then works as if it were studying a set of Targets (see below), and directive LIST may be used. You will then have the option to use more than one Probe in your GRID run, and will have several alternative output options, as defined by the values of directive LIST.
In summary, therefore, if you want to run a true single-Target computation, you should select the option: "individual (true)". On the other hand, if you want to run GRID using a pseudo-list of just one Target, you should select the option: "individual (pseudo)". Note that the pseudo mode must always be used when more than one Probe is required in a run on one Target.
46.5.1.2. When studying a set of targets
In this case Greater offers three alternative approaches:
You can create a list with all the GRINKOUT names of all the Targets, and this will produce one single GRINKONT output file for the whole batch.
You can run GRID individually using the individual names of each GRINKOUT file.
You can do individual GRID runs using a pseudo-list of one compound for each Target as described above.
Please note that choice 1 creates a single GRIDKONT file, containing all the fields for all Targets and all Probes. On the other hand, choices 2 and 3 created one GRIDKONT file for each Target:Probe combination. Choice 2 can be run for just one Probe and the output will then be in binary, while 3 is far more flexible.
Here is a table with some typical situations, and the recommended method for each:
46.5.2. Run action
Greater can be used to run GRID interactively, or it can produce a command file which may be used later for the proposed GRID run. (The command file is always called grid.in). This second option is useful if, for example, you plan to run GRID on a different computer than the one running Greater, or you want to do your GRID run overnight. When you study a set of Targets, this option also prepares a list file called greater.lst, which contains the names of all the Target files.
When you finally press OK, and if you have decided to run GRID interactively, Greater will immediately start running the GRID jobs in the background. If there is only one job, all the bar's status will be labelled "running..." until the whole process completes. On the other hand, when there are many jobs they will be started sequentially. In either case the Greater interface will be fully usable during computations, and the results for a Target can be inspected as soon as its computation has been completed, even if the overall computation is still ongoing for the other Targets. Any job already running will keep running after you exit from Greater, but no more jobs will be started after the running job has been completed.
46.5.3. Aborting a computation
Any interactive GRID run can be stopped from Greater by using the command: Compute->Abort or clicking the red Abort button in the toolbar. Computations in process are stopped without waiting for the associated programs to finish the current task, and the output files may therefore be incomplete.
46.6. Using the results of a GRID computation
Once GRID finishes computing the fields, Greater can be used to visualise the results or these can be exported to other formats in order to visualise them with other Molecular Modelling packages.
46.6.1. Visualising fields
Greater uses GVIEW to visualise structures and fields. From version 2.0 GVIEW is able to visualize virtually any type of GRIDKONT file.
To start GVIEW, select the Target which you intend to view; press the right mouse button and activate the command: "view fields". If the run has produced individual GRIDKONT files, this command will immediately show the field for the selected Target. If on the other hand GRID has produced one single GRIDKONT file for all Targets and Probes, this command "View Fields" will show the field for the first Target, and you will need to select any other Target within GVIEW by, for example, pressing <PgDn>).
Alternatively, you can press the command Target->View fields or use the View button on the toolbar. These actions are equivalent to selecting the first Target and then activating its visualisation.
46.6.2. Exporting fields to other applications
Greater can export its results only when it has been used to produce individual GRIDKONT files (eg. when the LIST directive has the value 1). The command: Targets->Export fields will ask the User for the output format which should be used. The available choices are:
ASCII (.txt)
Chem-X (.map)
InsightII (.grd)
Sybyl (.cnt)
Greater will then write a new file with the appropriate extension (.txt or .map or .grd or .cnt) for each Target, and will dump any messages about the file conversion into a file called: "export.log".
46.7. Saving and loading Greater computations
Greater can save the current programme status to a file which can be retrieved at a later date. This allows the User to repeat a computation without reimporting the Targets, redefining the box, etc. The saved files are written in a proprietary binary format. They are platform independent, and can be used across platforms. The format requires that the all the files involved (targets, kout files, etc...) are initially exactly in the same directory. If you have accidentally deleted or cleaned some files, you will need to reimport or rerun the computations.
To save the current programme status you should select the command File->Save computation or press the Save button on the toolbar and enter a suitable name. We suggest you use the extension .grib for saved Greater files.
To reopen a previously saved computation use the command File->Open computation or press the Open button on the toolbar and select the file. Alternatively, you can start Greater and load a previously saved computation like this:
Greater filename.grib |
where filename.grib is the name of the saved Greater computation.
46.8. PDB filtering details
Objectives
Make the final user importing the PDB structures by implementing a filter PDB file-cleaning, to optimise speed and reduce time consuming 'hand work'
Key ideas
A perfect filter is practically impossible to program. However, GRIN already makes a very good job detecting 'mistakes' in the PDB files. The filter should help the User to avoid dealing with small and recursive mistakes but not hiding real problems. The filter should be highly customisable. It should be also accessible and it should be possible to change the filtering levels from the import dialog.
Filter should allow the automatic import of correct PDB files from the PDB data bank, plus non standard file PDB from popular modeling programs like AMBER, InsighII, Sybyl, etc...
Common problems in importing phase:
| Common problem | Job of the filtering |
| Atoms or residues are present in the PDB, but appear as missing due to incorrect names and/or positions. | Incorrect atom and residues are renamed, using a set of predefined substitution rules, i.e.:
|
| PDB files coming from AMBER InsightII and SYBYL have some non standard peculiarities. | A set of substitution rules are used:
|
| Often the PDB does not include an OXT record before the TER record. | The position of the OXT is computed using the coordinates of O, CA and C. OXT record is then inserted into the PDB file. |
| Some atoms or residues appear two or more times in the file. These correspond to alternate positions in the crystal. | One of the alternate positions should be chosen and all the others should be moved into the _out file. Selection is based on the label of the residue name or checking the occupancy field and select the choice with highest factor. |
| Often GRIN complains about HIS hydrogens, because H have been included both at HIS positions D and E. | Both H are removed (to allow GRID to set them appropriately) or to keep both. Should be disabled when the remove H option is on. |
| PDB contains hydrogens that User doesn't need. | The filtering remove all the H. |
| PDB contains HETATM records that user don't need. | The filtering removes all the HETATM records. |
| PDB contains water molecules that user don't need. | The filtering removes all the water records. |
| Some atoms are missing | Not an easy solution is reported for the moment. |
The filtering approach
PDB files will be split into a _in and a _out files.
Filtering levels
GREATER implements four filtering levels:
| Name | GRIN LEVL | Filtering options |
| no filtering | - | - |
| automatic | 1 | All filtering option above reported ON |
| semi-automatic | 2 | Apply substitution rules ON Remove alternate positions OFF Remove HIS hydrogens OFF Remove hydrogens records OFF Remove HET records ON Remove water records ON |
| custom | customisable | Customisable |
These can be applied only to PDB files. Filtering levels different from 'no filtering' make the program to generate a filename_in.pdb and a filename_out.pdb files that are written to disk. GRIN runs on the filename_in.pdb.
The default filtering level and the filtering options can be selected in the third tab of the Selected options dialog:
Filtering options
1. apply substitution rules ON
This option activates the following operations:
- RULE1
if the element position of the atom name is 'D' then 'H' replaces it. This rule solves the problems with PDB including deuterium
- RULE2
Records with residue name equal to 'ACE' or 'NME' are moved to filename_out.pdb This rule was applied to solve the problem with AMBER PDB files
- RULE3
In records with residue name equal to 'ILE' and atom name equal to ' CD ', the atom is renamed ' CD1'.
- RULE4
In records with residue name equal to 'TRY', the residue name is renamed 'TRP'
- RULE5
If a TER record if found and the last residue does not contain an OXT record, a new OXT record is added. The position of the OXT is computed using the positions of the last CA, C and O atoms.
- RULE6
Records with atom name equal to 'Q' are moved to filename_out.pdb. This rule solves the problems with some PDB obtained by NMR
- RULE7
Records with atom name equal to 'LP' are moved to filename_out.pdb. This rule removes lone pairs lines inserted by SYBYL in some PDB files
2. remove alternate positions OFF
If the character at position 17 in an ATOM record is different from ' ' this character is assumed to be an alternate key label and subsequent records with a different alternate key are moved to the filename_out.pdb file. If a space is found, the key is reset.
3. remove HIS hydrogens OFF
Records with residue name equal to 'HIS' or 'HID' or 'HID' and atom name equal to 'H' are moved to filename_out.pdb
4. remove hydrogens records OFF
Records with atom name equal to 'H' are moved to filename_out.pdb
5. remove HET records ON
Records starting with the string 'HETATM' are moved to filename_out.pdb
6. remove water records ON
Records with residue name equal to 'HOH' or 'WAT' or 'DOD' are moved to filename_out.pdb
Testing reports
A test carried out on 100 PDB structures provides this result:
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