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The MakeDocks tab

1) Tab description:

The MakeDocks tab enables easy selection of the receptors, ligands and conditions used by AutoDock during docking. Depending on the origin of the grid maps used (obtained from either the CombineGrids tab or the MakeGrids tab), the user will or will not consider receptor flexibility during docking. At this point, note that the values the user has to write in the "Dimensions of the grids that AutoGrid previously built for the current receptors" and the "Minimum separation between two grid points (Å)" fields of this tab: (1) are common for all the receptors included in the list selected in the "Which receptors do you want to use?" field; and (2) must be the same as those used by AutoGrid when the grid maps for these receptors were built.

AutoDock's running conditions are read from a dpf file that is used as a model to build all the dpf files needed for the AutoDock runs that follow after pressing the "execute" button. We provide BDT users with one dpf file (i.e. model_GALS.dpf) for using the best AutoDock method (the Genetic Algorithm with Local Search; i.e. GALS) but they can easily edit it or build a new one with ADT to suit their specific needs or preferences.

The MakeDocks user also has to complete the "Dimensions of the grids that will use AutoDock" (which can be different from the dimensions of the "Dimensions of the grids that AutoGrid previously built for the current receptors" and are usually as large as possible in order to speed up make_docks, which is the program running under the present tab) and the "Security length (Å)" fields. Both parameters are only necessary when the receptor's area of interest is formed by more than one "partial box". To understand the meaning of these parameters, it is useful to know how make_docks controls where AutoDock runs (see the algorithm description).

 

 

If "Quantity of information sent" is set up to 5, then make_docks can e-mail to the users a PDB file every time make_docks stops working with one receptor. This file is not for analyzing results but it can be used as a record for future reference because it contains: (a) the coordinates of the self receptor; (b) a box showing the location of the receptor's area of interest; and (c) the different boxes inside the area where AutoDock has run (see below). This PDB file can be easily handled (e.g. coloured, hidden, etc.) by molecular graphic programs such as RasMol (Sayle and Milner-White, 1995) because coordinates from the receptor, from its area of interest or from the AutoDock boxes contained in this area are labelled as belonging to different subunits ("R" for the receptor, "T" for the area of interest and "P" for the AutoDock boxes).

 

2) Algorithm description for make_docks:

1) make_docks takes the input information provided by the MakeDocks tab
2) make_docks reads the coordinates of all the ligands that will be used during the docking and calculates the longest distance between any two atoms from these ligands.
3) make_docks obtains what we call the "maximum ligand length" by adding the "security length" value to the previously calculated distance. The reason for obtaining this "maximum ligand length" is that the coordinates of the ligand in the .OUT.PDBQ files (i.e. the ligands format in AutoDock) may not correspond to its most extended conformation (though it is strongly recommended that they do).
4) The number of points in the X-, Y- and Z-dimensions of AutoDock's maps (i.e. the contents of the "Dimensions of the grids that AutoGrid previously built for the current receptors" fields) and the minimum distance between two points in them (i.e. the contents of the "Minimum separation between two grid points (Å)" field) are used by make_docks to calculate the length of the shortest edge of the parallelepiped (which is not necessarily a cube) where each execution of AutoDock will run. From the difference between this value and the "maximum ligand length", make_docks obtains what we call the "stepsize".
5) make_docks selects the first receptor in the list and uses its pre-calculated grid maps to build all those that are needed for the first run of AutoDock.
6) After these maps are built, AutoDock tries to dock in them all the ligands from the list (one after the other). The results for this first run of AutoDock are conveniently labelled and stored for further use by the Analyze tab.
7) make_docks will repeat this process but in a parallelepiped that has been "moved" relative to the previous one by a distance that corresponds to the previously calculated "stepsize". Therefore, two adjacent AutoDock parallelepipeds always share enough volume to include (even in their more extended conformations) all the studied ligands. This ensures that ligand-binding sites in the interface between adjacent parallelepipeds are not lost during the blind docking.

Using this method, make_docks analyzes all the area of interest for the current receptor. It is important to note, therefore, that the larger the dimensions of AutoDock's grids, the larger the "stepsize" and, therefore, the fewer iterations needed to cover all the receptor's area of interest (i.e. make_docks runs faster).