- Autotors Commands: This Module facilitates selecting and formatting a ligand for a subsequent AutoDock run.
- The user selects the small molecule from a list of molecules already in the moleculeViewer OR as a PDBQ file or as a MOL2 file from a fileBrowser .
- The user selects the ROOT atom of the ligand either:
- by picking it
- by autoroot which sets the root to be the atom in the molecule which has the smallest 'largest sub-tree.'
- Next the user decides which possible and active torsions he wants to disallow, changing them from active to inactive. This is done by picking an active 'green' bond which turns it inactive or 'purple'. This is reversible. The user can also disallow all peptide backbone torsions and/ or all torsions of amide bonds.
- Carbons in cycles can be tested for aromaticity. If the angle between the normals to adjacent atoms in the cycle is less than 7.5 Degrees, the cycle is considered aromatic: its carbons are renamed "A.." and their element type set to 'A'. (This is for the force-field calculations done in AutoDock.) This Module does this conversion reversibly. Also, the user is able to select a carbon to convert (reversibly).
- Non-polar hydrogens can be merged which means that the charge of each is added to its carbon and the hydrogen atoms themselves are not written in the output file, thus in some sense 'removing' them from the molecule. 'Fewer' atoms simplifies the AutoDock run.
- The last function of this Module is to write a file which contains the correctly formatted ligand atoms. The ROOT section of the molecule expands from the selected ROOT atom out to include all atoms adjacent to it up to the first active torsion. The active torsions set the position of BRANCH and TORS key words in the output pdbq file (and their corresponding ENDBRANCH and ENDTORS key words). These keywords are nested to set up a Depth-First Order Traversal. Autotors also calculates the torsional degrees of freedom (TORSDOF) which is the number of possible torsions less the number of symmetry-equivalent torsions (such as a bond to a NH3). This key word is the last line of the pdbq file.
- Autogpf Commands: This Module facilitates producing a grid parameter file for AutoGrid. The steps in this process are:
- Selecting the macromolecule:
The user can select the macromolecule for autogpf in three ways:
- it can be chosen from molecules previously added to the moleculeViewer using the Choose Macromol... option
- it can be read in from a PDB file using the Read PDB Macromolecule option
- it can be read in from a MOL2 file using the Read MOL2 Macromolecule option
Selecting the types of maps to generate:
The user can set the types of maps to be generated by AutoGrid :by entering the types directly
by choosing a ligand
If a ligand is chosen or read in from a file, the types of atoms in it are then determined. If he wishes, the user can modify the set of atom types found. (NB: entries are activated by clicking the 'Return' key) Set Map Types Directly
Via Choosing Ligand
Via Reading PDBQ Ligand
Via Reading MOL2 Ligand
Setting the types of maps to be calculated:
At the same time the user sets the types of maps to be calculated, he decides which types of hydrogen bonding he wishes to model. For instance, if hydrogens are present AND nitrogens, oxygens and /or sulfurs, the user can decide to model N-H bonds, O-H bonds and/or S-H bonds. (Obviously, if there are no hydrogens present in the ligand, no hydrogen bonding should be modeled.)
The user positions the grid and sets its dimensions by:Setting the center of the grid maps: - by picking an atom
- - by entering the full-name of an atom
- - by entering the desired coordinates in entries 'x center', 'y center', 'z center' (NB: ALL entries must be 'activated' by a 'Return')
- - by choosing the 'autocenter' option which sets the center of the grid to the geometric center of the macromolecule (obtained by averaging all its coordinates)
Adjusting the position of the grid using scales for x-offset, y-offset and z-offset. These scales allow the user to move the grid box up to 10 angstroms in any direction along any of the three axes. (NOTE that the units of these scales are tenths of Angstroms and the new coordinates of the center are reflected in the x-center, y-center, z-center entries)
Additional parameters that the user could adjust: The smoothing factor can be changed from its default 0.5 Angstrom value. This changes the radius of the area within which the minimum energy is stored.
Electrostatic potential map may or may not be generated by AutoGrid.
Floating point potential map may or may not be generated
The user may decide whether or not to use the default distance dependent dielectric constant. If not, he can enter his desired dielectric constant or use the default value, 40. It should be noted that this entered value is multiplied by 0.1146 by the program for input to AutoGrid.
The grid parameters file:
The results of the previous steps are written to a file. The user selects a filename via a filebrowser. By convention, the file should have a .gpf extension. If no macromolecule has been selected, it is not possible to write a grid parameter file and the user gets a warning message to that effect. Likewise, the types of the maps to be calculated must be set before the grid parameter file is written and a warning message to this effect appears if the types have not been set. (A checkbutton, "DONE", allows the user to withdraw the autoTools menuBar and geometries used by this module or the autotors such as the box and spheres used to mark center of box if desired.)
- Autodpf Commands: This Module facilitates producing a docking parameter file for AutoDock. The steps in this process are:
- Selecting the macromolecule filename:
The user can select the macromolecule for autodpf in three ways:
It can be chosen from molecules previously added to the moleculeViewer using the Choose Macromol... option
It can be picked as a PDB file using the Select PDB Macromolecule option
It can be picked as a MOL2 file using the Select MOL2 Macromolecule option
Via Reading a PDBQ-File which adds the ligand to the viewer.
Setting parameters pertaining to the small molecule:
The user sets the parameters pertaining to the small molecule by :
- Checking that a grid map exists for each of the ligand atom types
- Indicating whether a floating grid map exists
- Setting the initial translation of the small molecule by: - choosing the 'random' option which sets a random starting position for the \ligand
- - entering the desired coordinates in the entry
- Setting the initial quaternion of the small molecule by: - Choosing the 'random' option which sets a random starting quaternion.
- - Entering the desired initial quaternion -Qx,Qy,Qz,Qw in the entry. Qx, Qy, Qz define the unit vector in the direction of rigid body rotation and Qw the angle of rotation about this unit vector. Setting the coefficient of the torsional DOF.
- Choosing to set the initial dihedrals for the small molecule or not: If not, AutoDock assumes that the chi1, chi2, chi3 etc are all zero and does not change the initial ligand torsion angles. If the user chooses to set the initial dihedrals, he further chooses: - for them to be randomly assigned
- - an initial relative dihedral angle for each active torsion in the ligand. The user can specify two types of torsion constraints for the ligand: - Gaussian constraints which use an inverted Gaussian bell curve to calculate the energy function input of the constraint. This type of constraint is specified by two floating point numbers: the perferred angle in the range -180-+180decreeds and the half-width which is the difference between two angles at which the energy is half the barrier PLUS an integer which identifies the torsion according to the list at the top of the AutoTors- generated input ligand PDBQ file. More than one constraint of this type may be specified for a single torsion.
- - Hard torsion constraints may also be specified. These differ from the previous type in that the torsion is never allowed to take values bewond the range defined and in that the second parameter is the full width of the allowed range of torsion angles.
- Moreover, only one constraint of this type is allowed per torsion. If the user specifies torsion constraints, he may also specify the height of the energy barrier to be applied to these constraints.
- If the user specifies Gaussian torsion constraints, he may also specify whether to store and output the torsion energies. It is important to remember that any of these may be used alone but only GA and LS may be used together.
The user sets parameters pertaining to docking algorithm(s) he wishes to use : o Setting Simulated Annealing parameters.
- - energy parameters including energy assigned to atoms outside the grid volume, the maximum allowable initial energy and the maximum number of retries.
- output format parameters including the level of detail for the output, the
rms cluster tolerance, the reference file for rms calculations and whether to
do symmetry checking in the rms calculations.
Saving the results to a file:
The results of the previous steps are written to a file. The user selects a filename via a filebrowser. By convention, the file should have a .dpf extension. If no macromolecule has been selected, it is not possible to write a grid parameter file and the user gets a warning message to that effect. Likewise, the types of the maps to be calculated must be set before the grid parameter file is written and a warning message to this effect appears if the types have not been set. (A checkbutton, "DONE", allows the user to withdraw the autoTools menuBar)
The steps in this process are:
The first step is the selection of the log file generated by an autodock job.
This module parses that file setting values in a dictionary 'docked' which is
an attribute of the molecular viewer.
These keys are set:
- 'macroFile' : the Macromolecule file used
- 'ligand' : the original ligand
- 'types' : the kinds of grid files used
- 'runs' : the number of docking runs
- 'clusterNum' : the number of clusters produced
- 'clusterList': a list of ADClusters which have members of ADDocked instances.
After the selected docking log file is parsed, the user can:
select a displayed docked conformation using the 'Choose A Docking'
menubutton. This opens a DockingChooser widget which is a ListChooser allowing
selection either in the widget or in the viewer of any of the displayed
docking. Information about each docked conformation is displayed in the
information window of the DockingChooser as different entries are high-lighted
display the macromolecule via the "Show Macromolecule" menubutton.
display the original input ligand via the "Show Original Ligand" menubutton. Both of these menubuttons are linked to file browsers in case the molecule parsed from the docking log file is not in the current directory.
Finally, the user is able to visualize a grid map using the "Show Grid" button. This will be linked to an isocontour utility. (currently not implemented)