2012 DOCK tutorial with Streptavidin

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For additional Rizzo Lab tutorials see DOCK Tutorials.

Use this link Wiki Markup as a reference for editing the wiki.

I. Introduction


DOCK is a molecular docking program used in drug discovery. It was developed by Irwin D. Kuntz, Jr. and colleagues at UCSF (see UCSF DOCK). This program, given a protein binding site and a small molecule, tries to predict the correct binding mode of the small molecule in the binding site, and the associated binding energy. Small molecules with highly favorable binding energies could be new drug leads. This makes DOCK a valuable drug discovery tool. DOCK is typically used to screen massive libraries of millions of compounds against a protein to isolate potential drug leads. These leads are then further studied, and could eventually result in a new, marketable drug. DOCK works well as a screening procedure for generating leads, but is not currently as useful for optimization of those leads.

DOCK 6 uses an incremental construction algorithm called anchor and grow. It is described by a three-step process:

  1. Rigid portion of ligand (anchor) is docked by geometric methods.
  2. Non-rigid segments added in layers; energy minimized.
  3. The resulting configurations are 'pruned' and energy re-minimized, yielding the docked configurations.

Streptavidin & Biotin

Streptavidin is a tetrameric prokaryote protein that binds the co-enzyme biotin with an extremely high affinity. The streptavidin monomer is composed of eight antiparallel beta-strands which folds to give a beta barrel tertiary structure. A biotin binding-site is located at one end of each β-barrel, which has a high affinity as well as a high avidity for biotin. Four identical streptavidin monomers associate to give streptavidin’s tetrameric quaternary structure. The biotin binding-site in each barrel consists of residues from the interior of the barrel, together with a conserved Trp120 from neighboring subunit. In this way, each subunit contributes to the binding site on the neighboring subunit, and so the tetramer can also be considered a dimer of functional dimers.

Biotin is a water soluble B-vitamin complex which is composed of an ureido (tetrahydroimidizalone) ring fused with a tetrahydrothiophene ring. It is a co-enzyme that is required in the metabolism of fatty acids and leucine. It is also involved in gluconeogenesis.

Organizing Directories

While performing docking, it is convenient to adopt a standard directory structure / naming scheme, so that files are easy to find / identify. For this tutorial, we will use something similar to the following:


In addition, most of the important files that are derived from the original crystal structure will be given a prefix that is the same as the PDB code, '1DF8'. The following sections in this tutorial will adhere to this directory structure / naming scheme.

II. Preparing the Receptor and Ligand

Downloading the PDB Structure (1DF8)

The Protein Data Bank contains atomic coordinates for more than 79,000 molecules and is accessible via the internet from PDB. The target (protein or nucleic acid) is accessible by PDB ID, molecular name, or author. After entering the PDB ID, molecule name, or author, click Download Files, then select PDB File (text). A window will open; click on Save File → Downloads.

Preparing the Ligand and Enzyme in Chimera

If you are on "herbie" you can access Chimera directly by typing in Chimera at the prompt. Otherwise, download Chimera to your desktop and obtain your protein/nucleic acid complex of interest Fetch (by ID).

Open Your Protein of Interest and Delete Unwanted Molecules:

Click on Open under the File menu and find where you saved your pdb file.

You only need one of the monomers to perform docking. Remove chain B by carrying out the following:

  1. SelectChainBAll.
  2. ActionsAtomsDelete.

To delete water molecules and/or other ligands, go to ToolsStructure EditDock Prep. Check all boxes and click okay. This will walk you through the steps needed to prepare the complex for docking, and will also assign partial charges to the protein and the ligand. Choose am 1-bcc for charges.

Save the file as 1DF8.dockprep.mol2.

dockprep image

This file contains a conformation of the complex with hydrogen atoms. The grid calculation is based on the receptor with its hydrogen atoms. The grid score is an energy calculation that is based on the following equation:

E GRID = E VDW + E ES. The score is an approximation of the molecular mechanics' energy function and it considers only through space interactions.

Create a Receptor File:

Go to SelectResidueBTN. Then go to ActionsAtomsDelete.

Save the file as 1DF8.receptor.mol2.

Create a Receptor File with No Hydrogen Atoms:

Go to SelectChemistryElementHDelete.

Save a PDB file as 1DF8.receptor.noH.pdb.

Create a Ligand File:

Open only the 1DF8.dockprep.mol2.

Go to SelectChainDelete. This will allow you to have only the ligand.

Save the file as 1DF8.ligand.mol2.

These are the files that you will need to continue with rigid or flexible docking.

III. Generating Receptor Surface and Spheres

Receptor Surface

To generate an enzyme surface, first open the receptor pdb file with the hydrogen atoms removed (1DF8.receptor.noH.pdb). Next, go to Actions -> Surface -> Show. Note that for DOCK calculation hydrogen atoms are considered, but for generating enzyme surface and spheres, it is necessary to use the protein without hydrogens.


Recent versions of Chimera include a Write DMS tool that facilitates calculation of the molecular surface. Go to Tools -> Structure Editing -> Write DMS. Save the surface as 1DF8.receptor.dms.


The Write DMS tool will "roll" a small probe (default radius = 1.4 Angstroms = Size of a water molecule) over the surface of the enzyme and calculate the surface normal at each point. DMS (distributed molecular surface) file is subsequently used as input file for sphgen.


To generate docking spheres, we need to use a command line program called sphgen. To run the sphgen, we need a input file named INSPH.

1DF8.receptor.dms            #molecular surface file that we got from previous step
R                            #sphere outside of surface (R) or inside surface (L)
X                            #specifies subset of surface points to be used (X=all points)
0.0                          #prevents generation of large spheres with close surface contacts(defalut=0.0)                        
4.0                          #maximum sphere radius in angstroms (default=4.0) 
1.4                          #minimum sphere radius in angstroms (default=radius of probe) 
1DF8.receptor.sph            #clustered spheres file that we want to generate

Save the INSPH file. Then use this command to generate spheres file:

sphgen -i INSPH -o OUTSPH

-i means input; -o means output.

You should get two output files: OUTSPH and 1DF8.receptor.sph. The OUTSPH file should similar to this:

density type = X
reading  1DF8.receptor.dms                                                     type   R
# of atoms =    881   # of surf pts =  10771
finding spheres for   1DF8.receptor.dms                                         
dotlim =     0.000
radmax =    4.000
Minimum radius of acceptable spheres?
output to  1DF8.receptor.sph                                                    
clustering is complete     28  clusters

You can also open the spheres file that we generated in this step (1DF8_receptor.sph). This file contains detailed information of the spheres, which are divided into 28 clusters. Cluster 0 in the end of the spheres file is a combination of all the clusters.

In order to visualize the generated spheres, you can use a program called showsphere. Showsphere is an interactive program. In the command line, simply type


You will be asked the following questions:

Enter name of sphere cluster file:
Enter cluster number to process (<0 = all): -1
Generate surfaces as well as pdb files (<N>/Y)? N
Enter name for output file prefix:
Process cluster 0 (contains ALL spheres) (<N>/Y)? N

In this case, 28 pdb files should be generated.

An alternative way to do this is to create an input file, showsphere.in, as follows:


Then type the command showsphere

showshpere < showsphere.in

After generating the pdb files by showsphere, you can visualize each cluster by UCSF Chimera. For example, open 1DF8.output_1.pdb by Chimera, then choose Actions->Atoms/Bonds->sphere, you will be able to see the spheres in cluster 1. You can also open the receptor file (1DF8.receptor.mol2) at the same time, then choose Presets->Interactive 3(hydrophobicity surface), then again choose Actions->Atoms/Bonds->sphere, you will be able to see what are the spheres in cluster 1 on the enzyme surface look like.


There are over 500 spheres in the spheres file(1DF8.receptor.sph). However, we're only interested in docking the ligand into the active site. Therefore we need to select only those spheres which are inside the active site, using sphere_selector program.

sphere_selector 1DF8.receptor.sph ../01-dockprep/1DF8.ligand.mol2 10.0

Sphere_selector filters the output from sphgen, selecting all spheres within a user-defined radius of a target molecule. In this case, we selected the spheres around 10 angstroms of our ligand. A file called selected_spheres.sph should be created, showing the spheres that are selected. You can again visualize it by showsphere. You can also change the radius (say 8 angstroms or 6 angstroms) or manully editing the file selected_spheres.sph so that you can select the spheres you want.

2012_DOCK_Tutorial_1DF8_surface_spheres_10 angstroms
2012_DOCK_Tutorial_1DF8_surface_spheres_6 angstroms

IV. Generating Box and Grid


In order to speed up docking calculations, DOCK generates a fine grid, and at each point in the grid electrostatic and a VDW probes' energies are precomputed. The energies are computed using a molecular force field. To determine the dimensions of the grid, however, we first generate a box that contains the outer boundaries for grid calculation. The dimensions and location of the box can be determined using a program called showbox.

First create a directory where you will place the grid files.

$mkdir 03-box-grid
$cd 03-box-grid

showbox can be used interactively or a file with predetermined answers can be fed into the program.

The program asks the questions depicted in the diagram the right:

Error creating thumbnail: Unable to save thumbnail to destination
Flow Chart of Questions for Showbox (Red path is followed in this tutorial)

To run the program in the interactive mode, run


To feed the answers to the questions, run

$showbox < showbox.in

For example, showbox.in can contain:


Y means we use automatic box construction, 5 is the extra margin to be enclosed around our ligand (in Angstroms), selected_spheres.sph is the sphere file we generated, 1 corresponds to the cluster number in the selected_spheres.sph file, and 1DF8.box.pdb is the output file. We can open the output box file in chimera to make sure the box is in the right place.

1DF8 receptor along with our ligand and the box we generated using showbox


Now let's generate a grid within our box. We will use the energy scoring method to generate a grid, resulting in three additional files with extensions *.nrg, *.bmp, and *.out. The *.nrg file contains the energy scoring, *.bmp contains the size, position and grid spacing and determines whether there are any overlap with receptor atoms.

To generate the grid we will use the grid program. This program can either be used interactively, or an input file can be fed in, just like the showbox program.

Usage: grid [-i [input_file]] [-o [output_file]] ...
 [-standard_i/o] [-terse] [-verbose]
 -i: read from grid.in or input_file, standard_in otherwise
 -o: write to grid.out or output_file (-i required), 
     standard_out otherwise
 -s: read from and write to standard streams (-i and/or -o illegal)
 -t: terse program output
 -v: verbose program output

For our grid.in file, we will use the following answers:

compute_grids                  yes
grid_spacing                   0.3
output_molecule                no
contact_score                  no
energy_score                   yes
energy_cutoff_distance         9999
atom_model                     a
attractive_exponent            6
repulsive_exponent             9
distance_dielectric            yes
dielectric_factor              4
bump_filter                    yes
bump_overlap                   0.75
receptor_file                  ../01-dockprep/1DF8.receptor.mol2
box_file                       1DF8.box.pdb
vdw_definition_file            /opt/software/AMS536software/dock6/parameters/vdw_AMBER_parm99.defn
score_grid_prefix              grid

Line by line:

  1. compute scoring grids (yes)
  2. what is the distance between grid points along each axis (in Angstroms).
  3. write up coordinates of the receptor into a new file
  4. compute contact grid? default is no
  5. compute energy score? yes - we are using this method to compute force fields on probes
  6. the max distance between atoms for the energy contribution to be computed
  7. atom_model u means united atom model where atoms are attached to hydrogens, and a stands for all-atom model, where hydrogens on carbons are treated separately
  8. attractive component stands for exponent of the attractive LJ term in VDW potential
  9. repulsive component stands for exponent in the repulsive LJ term in VDW potential
  10. distance dielectric stands for the dielectric constant to be linearly dependent on distance
  11. distance dielectric factor is the coefficient of the dielectric
  12. bump filter flag determines if we want to screen orientation for clashes before scoring and minimization
  13. bump_overlap stands for the fraction of allowed overlap where 1 corresponds to no allowed overlap and 0 corresponds to full overlap being permitted.
  14. our receptor file
  15. the box file we generated in the Box section
  16. VDW parameters file
  17. Prefix for the grid file name. All the extensions will be generated automatically.

V. Docking a Single Molecule for Pose Reproduction

Docking and Results

Change directory into “04-dock” and create an empty input file called dock.in

$touch dock.in     #create a file called “dock.in”

Run dock6.4

$dock6 -i dock.in


$dock6 -i dock -v # “-v” option allows you to print out the information regarding each growth step on terminal


$dock6 -i dock -o dock.bf.out -v # “-o” allows you to write the aforementioned information into an output file named “dock.bf.out”

1st run:

Notice that running dock6 with an empty input file will require you to answer a series of questions. For the first run we will deactivate most of the features by selecting “no”. Parameters requiring specification are listed below:

ligand_atom_file [database.mol2] ():   	../01-dockprep/1DF8.ligand.mol2
ligand_outfile_prefix [output] ():   		1DF8.output

What the program is doing in the 1st run is to take the ligand.mol2 file and directly generate an output file without any additional manipulations. You would expect it to be exactly the same as the original pose. You can open it in Chimera by using the “ViewDock” function under “Tools->Surface/Binding Analysis”. We will not show the result here.

2nd run:

The real experiment begins here. Notice that we selected “no” for most of the functions. This time we will try change some parameters in the dock.in file.

$vim dock.in

Parameters being changed are listed below:

orient_ligand                                               yes

The "orient_ligand" option tells the program whether to try orientations different from the pose in the original .mol2 file. Note that because of the change, additional questions are asked by the program. For simplicity we keep most of the answers as default. File paths requiring specifying are listed below:

receptor_site_file                          [receptor.sph] ():../02-surface-spheres/selected_spheres_06A.sph
vdw_defn_file                               [vdw.defn] ():../03-grid/vdw_AMBER_parm99.defn 
flex_defn_file                              [flex.defn] ():../03-grid/flex.defn 
flex_drive_file                             [flex_drive.tbl] ():../03-grid/flex_drive.tbl

The receptor_site_file should be the selected spheres file (.sph) generated in a previous step (02 surface and spheres), according which the program orients the ligand.

The vdw_defn_file instructs the dock6 program to use the Van der Waals parameter sets from the AMBER force field.

The flex_defn_file and the flex_drive_file contain the information required by the program to sample conformations.

The result is shown below. As you may notice the result doesn't look very good.

Example alt text
DOCK second Run result

3rd Run:

Here we will further specify parameters to improve the result.

calculate_rmsd                                               yes
score_molecules                                              yes
num_scored_conformers                                        10

Again, further questions will be asked when you run the program. Keep most answers as default. Paths requiring specification are listed below:

grid_score_grid_prefix                                        [grid] ():../03-grid/1DF8.grid

Note that the above specification will tell the program to load the 1DF8.grid.nrg file you generated in the previous step (grid) for scoring.

simplex_max_iterations                                        [1000] ():20
write_conformations                                           [yes] (yes no):no
cluster_rmsd_threshold                                        [2.0] ():0.2

The simplex_max_iteration parameter specifies number of minimization cycles.

Note the program will cluster poses that are very close together (rmsd smaller than the threshold specified in the cluster_rmsd_threshold parameter) into a cluster.

This time the program returned the best 10 poses. The one with the best grid score (-52.8, shown blue) superimposed quite well with the original pose in the crystal structure (RMSD = 0.71). You can view the grid scores in ViewDock by selecting “Column->Show->Grid Score”

Example alt text
DOCK third Run result

4th Run:

This time we will set the ligand as flexible:

flexible_ligand                                              yes

Further questions will be asked during the run. Keep most of the answers as default except for:

simplex_grow_max_iterations                                   [20] ():500

The simplex_grow_max_iteration specifies the maximum No. of iterations per cycle per growth step.

Notice that the run is significantly slower this time. Again the best pose generated (-64.8) is shown in blue. The grid score improved significantly but the RMSD did not change much (0.79)

Example alt text
DOCK fourth Run result

5th Run:

This time we will turn the bump filter on:

bump_filter                                                  yes

The bump_filter option filters out conformations that cause clash between atoms.

Further questions will be asked during the run. Keeps answers as default. Specify the following path:

bump_grid_prefix                                              [grid] ():../03-grid/1DF8.grid

Note that the path tells the program to access the .bmp file generated in the previous grid step.

The best pose (grid score -65.3) is again shown in blue. Notice that turning on the bump filter does not alter either the grid score or the RMSD (0.78).

Example alt text
DOCK fifth Run result

Remember you can tweak any parameter in the dock.in file instead of keeping them as default.

Following is the final dock.in file used during the fifth run:

ligand_atom_file                                             ../01-dockprep/1DF8.ligand.mol2
limit_max_ligands                                            no
skip_molecule                                                no
read_mol_solvation                                           no
calculate_rmsd                                               yes
use_rmsd_reference_mol                                       no
use_database_filter                                          no
orient_ligand                                                yes
automated_matching                                           yes
receptor_site_file                                           ../02-surface-spheres/selected_spheres_06A.sph
max_orientations                                             500
critical_points                                              no
chemical_matching                                            no
use_ligand_spheres                                           no
use_internal_energy                                          yes
internal_energy_rep_exp                                      12
flexible_ligand                                              yes
min_anchor_size                                              40
pruning_use_clustering                                       yes
pruning_max_orients                                          100
pruning_clustering_cutoff                                    100
pruning_conformer_score_cutoff                               25
use_clash_overlap                                            no
write_growth_tree                                            no
bump_filter                                                  no
score_molecules                                              yes
contact_score_primary                                        no
contact_score_secondary                                      no
grid_score_primary                                           yes
grid_score_secondary                                         no
grid_score_rep_rad_scale                                     1
grid_score_vdw_scale                                         1
grid_score_es_scale                                          1
grid_score_grid_prefix                                       ../03-grid/1DF8.grid
dock3.5_score_secondary                                      no
continuous_score_secondary                                   no
gbsa_zou_score_secondary                                     no
gbsa_hawkins_score_secondary                                 no
amber_score_secondary                                        no
minimize_ligand                                              yes
minimize_anchor                                              yes
minimize_flexible_growth                                     yes
use_advanced_simplex_parameters                              no
simplex_max_cycles                                           1
simplex_score_converge                                       0.1
simplex_cycle_converge                                       1.0
simplex_trans_step                                           1.0
simplex_rot_step                                             0.1
simplex_tors_step                                            10.0
simplex_anchor_max_iterations                                500
simplex_grow_max_iterations                                  500
simplex_grow_tors_premin_iterations                          0
simplex_random_seed                                          0
simplex_restraint_min                                        no
atom_model                                                   all
vdw_defn_file                                                ../03-grid/vdw_AMBER_parm99.defn
flex_defn_file                                               ../03-grid/flex.defn
flex_drive_file                                              ../03-grid/flex_drive.tbl
ligand_outfile_prefix                                        1DF8.output
write_orientations                                           no
num_scored_conformers                                        10
write_conformations                                          no
cluster_conformations                                        yes
cluster_rmsd_threshold                                       0.2
rank_ligands                                                 no

Now we will write up a script for submitting your dock job to Seawulf. Create a script called “sub.dock.csh”

$vim sub.dock.csh

wherein you write:

#! /bin/tcsh 
#PBS -l nodes=1:ppn=1 
#PBS -l walltime=01:00:00 
#PBS -o zzz.qsub.out 
#PBS -j oe 

cd ~/AMS536/DOCK_tutorial/05-dock_qsub 

/nfs/user03/sudipto/dock6/bin/dock6 -i dock.in -o dock.out 

This will request 1 processor from the cluster for your job. When you are submitting the job:

$qsub sub.dock.csh

Note that you might have to make the script executable before running it:

$chmod +x sub.dock.csh


VI. Virtual Screening

Virtual Screening Preparation

Virtual screening is a widely used method in computational drug design. It searches large libraries of chemical compounds to identify favorable structures that bind to a target molecule. To perform virtual screening, we use ligands.mol2, a mol2 file which contains 101 small molecules to be the virtual library. The computational cost is reasonable for a quick search. Usually we use larger molecule set from chemical database, such as ZINC(http://zinc.docking.org/).

Since the computational cost of virtual screening is much higher than sigle-ligand docking, it is better for us to run it on Seawulf. We need to compress the whole DOCK-Tutorial directory, copy it to Seawulf and compress it.

tar -cvf DOCK-Tutorial.tar DOCK-Tutorial/
scp DOCK-Tutorial sw:/nfs/user03/usrname/AMS536
tar -xvf DOCK-Tutorial.tar DOCK-Tutorial

Virtual Screening Protocol

The purpose of virtual screening is different from single molecule docking, so we need to modify our previous docking script dock.in to vs.in. We can see the difference between the two files.

< ligand_atom_file                                             ligands.mol2 
> ligand_atom_file                                             ../01-dockprep/1DF8.ligand.mol2 
< vdw_defn_file                                                /nfs/user03/sudipto/dock6/parameters/vdw_AMBER_parm99.defn 
< flex_defn_file                                               /nfs/user03/sudipto/dock6/parameters/flex.defn 
< flex_drive_file                                              /nfs/user03/sudipto/dock6/parameters/flex_drive.tbl 
< ligand_outfile_prefix                                        1DF8.vs.output 
> vdw_defn_file                                                ../03-box-grid/vdw_AMBER_parm99.defn 
> flex_defn_file                                               ../03-box-grid/flex.defn 
> flex_drive_file                                              ../03-box-grid/flex_drive.tbl 
> ligand_outfile_prefix                                        1DF8.output 
< num_scored_conformers                                        1 
> num_scored_conformers                                        10 
< cluster_conformations                                        no 
> cluster_conformations                                        yes 
> cluster_rmsd_threshold                                       0.2 

num_scored_conformers: 1 -> 10 In virtual screening, we only need the most favorable pose of each candidate molecule and compare them.
cluster_conformations: yes -> no Slightly different conformations are not clustered together. They are treated as different conformations in the docking process.

In order to generate different search spaces, we can modify some other parameters.

max_orientations: The maximal number of anchor orientations that will be generated.
min_anchor_size: The minimum number of atoms for an anchor.
pruning_use_clustering: Pruning conformations during the clustering process.
use_internal_energy: Using repulsive VDM to avoid internal clashes.

Parallel computing can reduce the running time of virtual screening. Here is our job submission script sub.virtual_screen.csh.

#! /bin/tcsh
#PBS -l nodes=4:ppn=2
#PBS -l walltime=01:00:00
#PBS -o zzz.qsub.out
#PBS -j oe
set nprocs = `wc -l $PBS_NODEFILE | awk '{print $1}'`
echo "Running on ${nprocs} processors"
echo ""
echo "processor list are:"
cd ~/AMS536/DOCK_Tutorial/06-virtualscreen
mpirun -np $nprocs dock6.mpi -i vs.in -o vs.out

Finally, we can submit the job and perform virtual screening.

qsub sub.virtual_screen.csh

Virtual Screening Results

After performing virtual screening on Seawulf or any other computer, if you are using a parallel computer, you should get a multi-mol2 file 1DF8.vs.output_scored.mol2 which contains the mol2 files of all succesfully docked ligands, a vs.out file which contains the dock results of successfully docked ligands, and vs.out.1 through vs.out.7 which contain dock results from different nodes you use (the number will vary according to the number of nodes you use, here we use 8 nodes as mentioned before).

The vs.out file is returned by the leading node and contains the information of each succesfully docked ligands, looks like this:

Molecule: ZINC33171556

Anchors:               1
Orientations:          500
Conformations:         116

   Grid Score:          -52.373383
     Grid_vdw:          -51.643253
      Grid_es:           -0.730129
   Int_energy:            6.125062

The vs.out.1 through vs.out.2 files are returned by other nodes processing those ligands, separately. For those succesfully docked ligands, the file will return the elapsed time for docking, and for those not succesfully docked, it will return an error massege like this:

Molecule: ZINC20605433

Elapsed time:  0 seconds

ERROR:  Could not complete growth.
        Confirm that the grid box is large enough to contain the ligand,
        and try increasing max_orientations.

If you download the multi-mol2 file from seawulf using:

scp sw:~/AMS536/DOCK_tutorial/06-virtual-screen/1DF8.vs.output_scored.mol2 ./

Now you have this multi-mol2 file 1DF8.vs.output_scored.mol2 on your local machine, you can actually open this file in Chimera to visually check you docking results and do some visual analysis. But it's not a good idea to directly open your multi-mol2 file because it contains information of all 47 succesfully docked ligands, if you just open this file, it will be pretty messy. So what you will do is, first you open the receptor file 1DF8.receptor.mol2 and the ligand 1DF8.ligands.mol2 as a reference. And then use the ViewDock function of Chimera to look at your 47 ligands one or however many you want at a time. You can find ViewDock via Tools -> Surface/Binding Analysis -> ViewDock, and then find your 1DF8.vs.output_scored.mol2 file in your own directory and click on open. Now a new window of ViewDock will pop out and there will be an extra ligands in Chimera main window which is the highlighted ligand in ViewDock window. You can look at the ligands one at a time, you can also hold ctrl and click on different ligands to view them at the same time, this will give you a direct idea of how good these ligands dock. The other thing you can do is, the multi-mol2 file 1DF8.vs.output_scored.mol2 contains the energy score of every ligand, so in ViewDock window, you can go to Column -> show -> Grid Score to show the grid score, and then you can click on the head of the column to rank order all the ligands by their grid scores.The picture showing here is the best and worst scored ligands of out calculation, the best scroed one in cyan and the worst scored on in magenta, and the reference ligand is colored according to elements. As you can see, the best scored ligand fits in the binding pocket very well, but the worst scored one almost sticks out of the binding pocket.

Example of Virtual Screening Result

VII. Running DOCK in Serial and in Parallel on Seawulf

The Seawulf Cluster has 235 dual processor nodes (2 processors per node), for a total of 470 individual processors. These are 3.4Ghz Intel Pentium IV Xeon processors from Dell. Each node has 2GB attached RAM and a 40GB hard disk.

Typically you will use one processor on a single node to dock one ligand. If you are docking multiple ligands, you can use more than processor in parallel mode, but you should never use more processors than you have ligands.

Running DOCK in Serial on a Single Processor

The following sample code can be used to run DOCK on one processor on a single node:

#PBS -l nodes=1:ppn=1        
#PBS -l walltime=01:00:00   
#PBS -N dock6           
#PBS -M user@ic.sunysb.edu 
#PBS -j oe                   
#PBS -o pbs.out            

cd /nfs/user03/sudipto/DOCK_Tutorial                     
/nfs/user03/sudipto/dock6/bin/dock6 -i dock.in -o dock.out

Here is an explanation of the code and format:

#!/bin/tcsh                                                 #Execute script with tcsh
#PBS -l nodes=1:ppn=1                                       #Use one node, and one processor per node, so one single processor 
#PBS -l walltime=01:00:00                                   #Allow 1 hour for your job run
#PBS -N dock6                                               #Name of your job
#PBS -M user@ic.sunysb.edu                                  #Get an email notifying you when your job is completed
#PBS -j oe                                                  #Combine the output and error streams into a single output file
#PBS -o pbs.out                                             #Name of your output file

cd /path-to-your-home-directory-on-seawulf/DOCK_Tutorial    #Change to your home directory and folder with dock files                  
/nfs/user03/sudipto/dock6/bin/dock6 -i dock.in -o dock.out  #Specifies path to dock executable and provide input and output filenames

Running DOCK in Parallel using MPI

The following sample code can be used to run DOCK on 4 nodes, using both processors on each node, for a total of 8 processors.

#! /bin/tcsh
#PBS -l nodes=4:ppn=2
#PBS -l walltime=24:00:00
#PBS -o zzz.qsub.out
#PBS -j oe

set nprocs = `wc -l $PBS_NODEFILE | awk '{print $1}'`

echo "Running on ${nprocs} processors"

cd /nfs/user03/sudipto/DOCK_Tutorial
cp /nfs/user03/sudipto/dock6/parameters/vdw_AMBER_parm99.defn .
cp /nfs/user03/sudipto/dock6/parameters/flex* .

mpirun -np $nprocs /nfs/user03/sudipto/dock6/bin/dock6.mpi -i dock.in -o dock.out

For more information, see PBS Queue

Serial Calculation for Pose Reproduction

Parallel Virtual Screen

VIII. Frequently Encountered Problems


Woo Suk

Distinguishing overlapped spheres

Sometimes your 1DF8.output_1.pdb can have some overlapped spheres. In this case, you cannot find them before you delete one sphere and you have to repeat this one more time to delete another one.
In order to avoid the situation, you can adjust a parameter in INSPH file like following:


You can change the fourth parameter from 0.0 to other values such as 0.1, 0.01, or 0.001. Because what you want is just to distinguish the very close spheres, you don't need large numbers.

Long Fei







Delete Spheres Manually

We need to play some tricks if we want to manually select the spheres in selected_spheres.sph.

1.Transfer sph file to pbd file by using showsphere.
2.Open the pdb file in Chimera and choose the sphere we want to delete.
3.Identify the number of that sphere by Actions->Label->residue->specifier
4.Open sph file, delete that sphere and modify the number of spheres in that cluster.

DOCK spheres within 6.0 ang of ligands
cluster     1   number of spheres in cluster    22
  60  28.86000  11.09173   4.97943   2.337  586 0  0
  67  28.67840   9.74620  12.13940   1.400   60 0  0
 161  27.11509  13.42709  13.48051   1.401  385 0  0
 174  27.79940  12.82468  12.04078   2.475  480 0  0
 183  34.13903  14.01393   7.31591   3.590  691 0  0
 187  36.78641  17.02434   9.54436   3.481  691 0  0
 385  30.01753  14.79655  14.46633   1.402  174 0  0
 463  25.74631  14.83304   9.98248   1.400  589 0  0


Keeping your data in sync

One problem you may encounter is that you want to run your jobs on Seawulf, but you also want the same files on a mathlab computer (or your home computer) for analysis. One option is to use RSYNC to keep your files on Seawulf and Herbie (or any mathlab computer) in sync. For example, if you want to move your DOCK Tutorial files to Seawulf, do the following from Herbie or any mathlab computer:

rsync -arv /home/username/DOCK_Tutorial/ sw:/nfs/user03/username/DOCK_Tutorial
  • Note: The trailing slash on /home/username/DOCK_Tutorial/ means that rsync will only copy the contents of your DOCK_Tutorial folders. If you want to copy the DOCK_Tutorial folder itself, as well as its contents, then remove the trailing /.

To copy newer files from Seawulf back to Herbie, do the following from Seawulf:

rsync -arv /nfs/user03/username/DOCK_Tutorial/ username@compute.mathlab.sunysb.edu:/home/username/DOCK_Tutorial

You can apply this same strategy to then sync files with your home computer as well. Use the following format:

rsync -arv source target
  • Note: this is easiest if you are using a Linux or Mac computer at home.

Deleting jobs

If you make a mistake and need to delete a job from the queue, first list all your queued or running jobs:

qstat -u kip
  • IMPORTANT: If you get no output from qstat, it means that whatever jobs you have submitted are done!

If you do have jobs running or waiting in the queue, qstat will output a list that includes their job id(s). Find the job id for the one you want to delete, and do:

qdel jobid