Header image  
Biologic Software  
line decor
  
line decor
 
 
 
 

 
 
The Analyze tab

1) Tab description:

The Analyze tab can be used to analyze the docking results (e.g. by comparing the docking of different ligands onto the same receptor, etc.). From this tab, the user can select or set up: (1) the ligand-receptor pairs whose docking results will be analyzed; (2) the docking energy threshold below which a docking result for a ligand is rejected; (3) the root-mean-square deviation threshold used to cluster docking results for the same ligand (where the one with the highest receptor affinity is chosen as the cluster representative); (4) the width of the interval used in the RasMol (Sayle and Milner-White, 1995) scripts to colour cluster-representatives according to their receptor affinity; and (5) how many cluster representatives will be considered for each ligand. Once all this information is set up, the Fortran program under this tab (i.e. analyze) can be started.

 

2) Algorithm description for analyze:

1) analyze takes the input information provided by the Analyze tab
2) analyze takes the first receptor from the list and generates a PDB file with its coordinates and with those from the box that corresponds to its studied area of interest
3) analyze  takes all the output files corresponding to the docking of the first ligand into the current receptor and extracts the coordinates for all the predicted conformations of the ligand in its complex with this receptor.
4) All the ligand conformations whose docking energy is more positive than the corresponding user-defined threshold are rejected and the remaining ligand conformations are then clustered. Each cluster is therefore represented by the coordinates that correspond to the one with the highest affinity for the receptor.
5) The various cluster representatives are sorted according to their receptor affinity (i.e. the coordinates for the one with the highest affinity are labelled with the number one, and so on) and their coordinates are written into the PDB file that already contains the coordinates from the receptor and box showing its area of interest.
6) Steps from 3 to 5 are carried out with the output files that correspond to the docking of the other selected ligands onto the current receptor.
7) Two RasMol scripts are written to make it easier to compare the docking results of the different ligands onto the same receptor. The first one (i.e. script_01) colours the ligands according to different intervals of affinity for the receptor irrespective of their identity (i.e. from hot to cold colours for decreasing affinity) and is therefore useful for identifying where the most important ligand-binding sites in the receptor structure are located. The second one (i.e. script_02) colours the ligand according to its identity and is therefore useful for comparing the specificity of the different ligands for each binding site.
8) Once all the docking results for one specific receptor have been analyzed, the corresponding PDB file and Rasmol scripts are sent to the user e-mail address for further analysis with Rasmol. All this process is repeated with every receptor in the list.

 

 

3) Description of the output PDB file:

The output PDB files from analyze have the following parts:
  1) Receptor coordinates
    This is the first part of the output PDB files. It contains the coordinates for all the atoms in the pdbqs file (usually atoms from protein or nucleic acids but sometimes also from cofactor, water molecules, etc). The coordinates are identified with the label "R" in column 22 of the PDB file and can be easily selected with RasMol by using the command "select *R".
  2) Total box coordinates
    This is the second part of the output PDB files. It contains the coordinates of the box where the docking of the different ligands onto the receptor has been analyzed (i.e. the receptor's area of interest). The coordinates are identified with the label "T" in column 22 of the PDB file and can be easily selected with RasMol by using the command "select *T". The total box coordinates are connected by CONNECT records.
  3) Ligand coordinates
    This is the third part of the output PDB files. It contains the coordinates of the cluster-representatives obtained from the docking of the various ligands onto the receptor. The coordinates are grouped according to the following criteria:
        • All conformations belonging to the same ligand are grouped and the ligands are identified in columns 18-20 with their corresponding labels. They can be easily selected with RasMol by using the command "select [LAB]" (where LAB must be replaced by the three-character label of the corresponding ligand).
       

• All the coordinates for one specific conformation of a ligand are labelled with the same ligand label in columns 18-20 and with the same conformation number in columns 23-26. VERY IMPORTANT: The docking energy onto the receptor is found in columns 69-76 (whereas the integer part of this energy is located in the same columns in which the "B-factor" values are found in standard PDB files). Therefore, using the RasMol command "select temperature < -11", it is possible to select all cluster-representatives with energy more negative than -11.00 Kcal/mol. Other comparison operators that can be used with the "select temperature" command are >, <= and >=.

        • The various conformations for one specific ligand are sorted according to decreasing affinity for the receptor. Thus, the conformation with highest receptor affinity is labelled "1" in columns 23-26, the conformation with the second highest receptor affinity is labelled "2", and so on.

To use this two RasMol scripts, please put them in the same folder where RasMol looks for the PDB files and load them with the command "script NAME" [where NAME must be replaced by the complete name of the script (including the file extension, if any)]