AutoDock 4 - Science topic

Your .dlg file indicates that your docking simulation is not completed successfully. You need run autogrid step and just check your .map other files (.fld, .xyz) are prepared properly.

I agree, the memory leak warning does not make a difference. The docking works fine.

Ya there was some problem and it was now solved. Thanks for your answer.

Use MultiDock Screening Tool

Use MultiDock Screening Tool

https://yogeshgaikwad- labhelper.github.io/multidockweb.github.io/index.html

Use MultiDock Screening Tool

https://yogeshgaikwad- labhelper.github.io/multidockweb.github.io/index.html

Looking at the code provided related to your error message, it seems that there are no residues left detected which have no action torsion left. Therefore, I assume it could not processed what you want to do for now.

Hello Ferlyn Macapagal De Jesus,

I have the same problem, did you figure out how to add atom types to ADFR? Thank you!

Each program has its own definition of a hydrogen bond. It is only a strong hydrogen bond with a distance closer than 3.0 A and an appropriate angle being shown consistently in all the visualization programs. Therefore, at your own assessment, you should choose which visualization program to use, but anyway it should be consistent throughout your report/article/thesis.

Did you install mgltools before installing autodock ? It contains certain commands that support autodock visualizations. You should try installing MGLtools and then re-install autodock. with updated versions

Julia Gomes

Upon downloading the source code you have to change the "MAX_ATOMS" value in the "constants.h" file from 32 to any desired number (I have a version with 64 MAX_ATOMS and it works fine).

Compiling is well described in the README file of the autodock suite and it depends in your machine, but I did the usual steps on my CENTOS (./configure, make, make install) and had no problems.

The error suggests an issue with the `broken` list in the `_formatstodict` function of `pybel.py`.

Try updating the `pybel` package to a compatible version by running the following command in your terminal:

```bash

(vina) gorrie06@DMGLaptop:~/docking/covalent$ pip install --upgrade pybel

```

This command will upgrade the `pybel` package to the latest version available. After upgrading, try running the `prepareCovalent.py` script again to see if the issue is resolved.

If the issue persists or upgrading `pybel` doesn't work, you can try using an alternative approach to run the covalent docking tutorial. Instead of using the `pybel` package, you can use the `rdkit` package, which is a powerful cheminformatics library that can handle various file formats, including PDB files.

To use `rdkit` in your script, you will need to install it by running the following command:

```bash

(vina) gorrie06@DMGLaptop:~/docking/covalent$ pip install rdkit

```

Once `rdkit` is installed, you can modify the `prepareCovalent.py` script to replace the `pybel` import and related code with the corresponding `rdkit` code for reading PDB files. Here's an example of how you can modify the script:

1. Open the `prepareCovalent.py` script in a text editor.

2. Remove the line `import pybel`.

3. Replace the line `ligand = pybel.readfile("mol2", ligandfile).next()` with the following code:

```python

from rdkit import Chem

ligand = Chem.MolFromMol2File(ligandfile)

```

4. Replace the line `receptor = pybel.readfile("pdb", receptorfile).next()` with the following code:

```python

receptor = Chem.MolFromPDBFile(receptorfile)

```

5. Save the modified script.

With these modifications, the script should now use `rdkit` instead of `pybel` for reading the ligand and receptor files. This should resolve the issue you encountered with `pybel` and allow the script to read the PDB file correctly. Make sure you have the `rdkit` package installed in your Anaconda environment (`vina`) before running the modified script.

Good luck: partial credit AI

The reasons for control docking/ redocking more than 2 Å might due to:

1. Not included all the important amino acids in the box.

2. The protein protonation at the pocket or ligand charge, but if you follow the standard protocol, it should be no problem.

3. You might need to check for ligand interactions. If there is a covalent bond, you might need to use the covalent bond protocol.

To get the RMSD below 2, you might need to reevaluate the box size/parameters.

hello

I guess you might have made mistake during preparation step or alloting the workspace.... Please do verify these things.... You can refer to tutorials in youtube as well..

Regards

You would be right, the cyclodextrin is not meant to be a typical receptor but I was wondering if the autodock software by any chance could read it as such. The beta cyclodextrin is used to encapsulate other hydrophobic substances like drugs with such properties. That’s why I was asking this question. If I find anything I’ll let you know too. Thank you for your response either way I appreciate it.

To batch ligand PDBQT input files to AutoDock 4, you can utilize a scripting or programming language to automate the process. Here's a general approach:

import os # Specify the directory containing the ligand PDBQT files ligand_directory = "path/to/ligand/files" # Get a list of all ligand files in the directory ligand_files = os.listdir(ligand_directory) # Loop through each ligand file and run AutoDock for each for ligand_file in ligand_files: # Generate the command to run AutoDock for the current ligand file command = f"autodock4 -p receptor.pdbqt -l {os.path.join(ligand_directory, ligand_file)} -o {ligand_file}.dlg" # Run the AutoDock command os.system(command)

Make sure to replace "path/to/ligand/files" with the actual directory path where your ligand PDBQT files are located. Also, adjust the AutoDock command (autodock4) according to your specific requirements, including specifying the receptor file (receptor.pdbqt), output file name ({ligand_file}.dlg), and any other options you need.

python batch_autodock.py

The script will loop through each ligand PDBQT file in the specified directory, run AutoDock for each ligand using the receptor file, and generate the corresponding output files.

Note: Make sure AutoDock 4 is properly installed and accessible in your system's PATH for the script to execute the AutoDock command successfully.

This approach allows you to batch process multiple ligand PDBQT files with AutoDock 4, saving you time and effort compared to running the commands individually.

Performing docking analysis for a protein-ligand complex is not exactly going to give comprehensive explanation on an activity potential. Like the routine goes, you identify the activation site then build a pocket around it to predict a poses (Rigid or flexible) that the ligand can form to sit well in the site, then score them based on RMSD for affinity strength. If you notice this condition, only the activation site is essential for this two function (pose forming and scoring). So if your protein structure is to have a mutant amino acid residue outside this box it has no influence in the docking profiling. Nonetheless, docking is not exactly a functional evaluation because the several other biochemical and chemical conditions that is needed is not present, the algorithm only mimic for structural effect.

If you need to do more on mutant functional effect on disease condition then that's a different analysis to pick on.

This is an intriguing question. First, defining the protein's binding pocket by setting the grid box does not necessarily stop the ligand from interacting with other residues outside the grid box. Hence, mutating the residue in silico could have a potential impact on the docking scores which would be a major criterion in screening out the small molecules.

Also, taking into consideration the charge of the wildtype and mutant proteins, the modification of the protein would perturb the charge of the protein and could potentially have an impact on the interaction profiles of the protein with the compounds.

It will be good to perform both pre- and post-modification docking on the protein to take into account the potential impact of the residue change. Furthermore, I would advise you to get the sequence of the protein and conduct homology modelling using the crystal structure you currently have as the template as opposed to conducting modification using software like Chimera and PyMol.

Our group experienced the same problem. Please let us know the solution in case it is solved. Thank you.

Let you have the PDB file of the alpha subunit, open it with notepad,

1) at the end of chain A, write TER to terminate the chain.

2)then paste the coordinates of the beta subunit (from the source beta subunit pdb file)

3) also paste the connectivity section (CONECT) of beta subunit after the alpha chain CONECT part.

4) END

Have you looked at your pdb file in a text editor and in a molecular viewer? Potential sources of this error are - alternative conformation, multiple chains with the same chain label, duplication in your residue selection. Have a close look at the N-terminal residue of chain A to get to the source of the problem.

Uninstall mgltools and all assoicated softwares. Then reinstall.

The parameters for Si are mentioned below

atom_par Si 4.30 0.402 12.175 -0.00110 0.0 0.0 0 -1 -1 4 # Non H-bonding

Copy and paste in the AD4_parameter.dat file. (align the values correctly). Next, you need to keep the modified bat file to the folder where the autodock.exe and autogrid.exe files are. Then you need to modify the .gpf and .dpf files by adding "parameter_file AD4_parameters.dat" command as shown in the attached screenshot.

Happy docking !!!

If you are using PyRx interface for screening (Autodock Vina module), do energy minimize all the ligands and the protein prior to screen. This will do the job........

Regards

during ligand preparation there is the the -Z and -I flags:

-Z inactivate all active torsions (default is leave all rotatable active except amide and guanidinium)"

[-I] string of bonds to inactivate composed of " print " of zero-based atom indices eg 5_13_2_10 " print " will inactivate atoms[5]-atoms[13] bond " print " and atoms[2]-atoms[10] bond " print " (default is not to inactivate any specific bonds)"

Hi,

This topic has been discussed in Researchgate community:

Article Titanium dioxide nanoparticle-protein interaction explained ...

Article Docking of HIV protease to silver nanoparticles

Hello, I had the same problem, but I solved it.

When you open and use AutodockTools, you follow the path "File\Preferences\Set\Startup Directory" and add the folder you are working in.

If you delete the folder you are working in after you have finished working, then when you open the application again, it gives this error because python cannot find the path to the folder.

Solution 1: Use a folder you always work in and don't delete or move it.

Solution 2: Before closing AutodockTools, restore the folder you last used or create a new folder with the same name.

Note: If you can't open the application and you can't do solution 2, uninstall AutodockTools and install again, pay more attention to this topic (solution 1) in your next work!

I hope it was enough.

Seçkin KAYA

It is really interesting question. If the visualization is correct, the interaction in first image is ionic interaction and electrostatic interaction in second imagine

Yes. The programs/subroutines that do the calculations do this based on the properties of the individual atoms, independent of the bond model. There is no localised +1 charge on the nitrogen, which you would have in the protonated nitrogen, but the lone electron pair of the nitrogen is part of the aromatic pi electron system.

Hi,

is it this one?

RCSB PDB - 1R42: Native Human Angiotensin Converting Enzyme-Related Carboxypeptidase (ACE2)

Martin Klvana I cant run the script. I can't open the bash file on my laptop to run the script. I guess there must be an error in the path to open the respective files.

Dear Dr Shadreen Fairuz

Please kindly go through this page, hope it can help you.

Dear Yassine Aimene

Using AutoDock 4 with ADT

http://autodock.scripps.edu › 2012_ADTtut

Dear Winnie Wen

When swig/python detects a memory leak of type ‘BHtree’, this type of error occurs. But, it does not affect the docking as no destructor found. I hope you got your answer.

In the linux terminal, run the following command:

autogrid4 -p name.gpf -l name.glg

it will generate the grid log file (glg) that will be used in the docking step.

Best,

Hey,

First, try to recalculate the grid maps with AutoGrid4. It should solve your problem.

If the first step doesn't work, while defining map types (Set Map Types option) there should be an atom list like "A C HD N ...". Add the missing atom here manually and calculate grid again. That will produce the missing map there.

Cheers

Ali

Hi,

here is an example:

outlev 1 # diagnostic output level

intelec # calculate internal electrostatics

seed pid time # seeds for random generator

ligand_types C OA N NA HD # atoms types in ligand

fld abc_transporter.maps.fld # grid_data_file

map abc_transporter.C.map # atom-specific affinity map

map abc_transporter.OA.map # atom-specific affinity map

map abc_transporter.N.map # atom-specific affinity map

map abc_transporter.NA.map # atom-specific affinity map

map abc_transporter.HD.map # atom-specific affinity map

elecmap abc_transporter.e.map # electrostatics map

desolvmap abc_transporter.d.map # desolvation map

ligand mol1.pdbqt 2.8610 -2.5460 4.0180 # small molecule 1

ligand mol2.pdbqt 1.3392 -0.1361 0.0435 # small molecule 2

ligand mol3.pdbqt 1.8610 -4.5460 0.0180 # small molecule 3

mlsd init # read pdbqt rec and init

tran0 random # initial coordinates/A or random

quaternion0 random # initial orientation

dihe0 random # initial dihedrals (relative) or random

torsdof 20 # torsional degrees of freedom

rmstol 2.0 # cluster_tolerance/A

extnrg 1000.0 # external grid energy

e0max 0.0 5000 # max initial energy; max number of retries

ga_pop_size 150 # number of individuals in population

ga_num_evals 5000000 # maximum number of energy evaluations

ga_num_generations 25000 # maximum number of generations

ga_elitism 1 # number of top individuals to survive to next generation

ga_mutation_rate 0.02 # rate of gene mutation

ga_crossover_rate 0.8 # rate of crossover

ga_window_size 10 #

ga_cauchy_alpha 0.0 # Alpha parameter of Cauchy distribution

ga_cauchy_beta 1.0 # Beta parameter Cauchy distribution

set_ga # set the above parameters for GA or LGA

sw_max_its 300 # iterations of Solis & Wets local search

sw_max_succ 4 # consecutive successes before changing rho

sw_max_fail 4 # consecutive failures before changing rho

sw_rho 1.0 # size of local search space to sample

sw_lb_rho 0.01 # lower bound on rho

ls_search_freq 0.06 # probability of performing local search on individual

set_psw1 # set the above pseudo-Solis & Wets parameters

ga_run 100 # do this many GA runs

analysis # perform a ranked cluster analysis

Hope it helps!

Well I use MGLTools 1.5.6, and working!

Here is the link http://mgltools.scripps.edu/downloads

You can download anything depends on your OS.

How-to dock a ligand with many torsions

For AutoDock4 systems with more than 10-12 torsions require special treatment. AutoDock Vina is successful with systems up to about 20 or so torsions. Using AutoDock Vina to dock systems with more torsions may require special treatment, too.

Two approaches to try are:

Nayan Prajapati

1. iGEMDOCK & Autodock Vina are widely used during the virtual screening process (where you have more number of compounds to dock to a protein). The process is simple and one after molecule is automatically screened.

2. Autodock vina requires few command line and manual operations, however, you can use GUI versions like pyrx, racoon, etc.

3. Autodock vina usually don't have results visualization directly, however you can use external software like pymol or discovery studio to analyse your results.

4. The efforts needed in iGEMDOCK is pretty lesser where you get results in a few clicks.

5. AutoDock is usually used in the case of grid-based docking where you wish to see to long performance rather just screening. A long run with multiple conformations will give you an idea on understanding the involvement of crucial amino acids and other bond formations.

6. As of today, AutoDock4 has 10974 citations, AutoDock vina has 13262 citations, and iGEMDOCK has 528 citations.

Considering these, you have to choose the tool based on your necessity and can't be one single conclusion. Even the forcefield parameters differ from one to another. However, on the whole, the molecular dockings itself have a huge set of known limitations like they predict molecules in static condition but the real system is not static. So, in the end, you need to perform molecular dynamics simulations to validate your dockings.

may be check the name of your ligand if it long you face this problem. I got this problem and fix this way.

Uttam Pal A few things I've figured out. AutoDockTools will not generate all the map files Raccoon expects. I need to add additional e.g., <xxx>.Br.map by hand even though the receptor does not contain that atom type.

But that aside, I'm still getting lots of problem. Please see this question to:

https://www.researchgate.net/post/Autodock_Raccoon-why_is_it_throwing_a_python_error

Tushar Dhyani

Will please send me the complete error details?

Hi,

There is possibility to comparison between Autodock4 and Autodock vina. Because the difference between these 2 programs is only in scoring functions.

As #Paulo Sérgio Alves Bueno mentioned earlier.

Hi Saiful,

Check the following Researchgate archive:

you can do a blind docking in Arguslab software but if you patient auto dock is good

just ignore it . it doesn't make huge difference usually.

Hi Sourav,

Try Protein-Ligand Interaction Profiler server:

https://projects.biotec.tu-dresden.de/plip-web/plip/help

Hello

have a look at http://click2drug.org for an updated list (with links) of docking softwares.

Yes, Discovery studio is good.

Just import both of them into the project table. Include both of them in the workspace. That's it.

But I guess Maestro can't read .pdbqt format which is default in Autodock. So, when you run a docking job in Autodock, make sure you export the results in .pdb format, not .pdbqt

MCF-7 is a breast cancer cell line which was obtained from a patient. It was not engineered to overexpress a particular protein or pathway. So, you can't relate MCF-7 activity to one particular target. However, since your compounds are active on MCF7 cell line, you can present it as inhibitors of MCF7 cells proliferation.

Now for target identification, you have to biotinylate your compound and do protein pull down studies. This is a definitive method for target identification. If you don't have the infrastructure for protein pull down or a collaborator who can do that, you could 'suggest' the 'probable' targets based on computational approaches. Do a literature search on which compounds are similar to the ones you have, and see their biological activity profile. Then dock your compounds to that target.

Hope this helps.

You should use AutoDock 4, because AutoDock Vina does not handle metalloproteins well.

Or, I recommend trying idock, which can handle many metalloproteins and dock ligands very quickly:

You can use the same configure file as AutoDock Vina.

First and foremost, one is supposed to check the physiological state of the protein prior to docking/MDS. Subsequently, one can decide which chain to keep and which to discard. There is no harm in keeping the entire protein chains while performing docking/MDS, except the computational cost. One more thing, better mimicking of the biological molecules can be done by performing MDS.

Of course, you can go with the drug-likeness (Lipinski's rule of five and Veber rule) and ADMET filtering. Moreover, you can set a threshold for the docking score based on the docking score of the known drugs or inhibitors against the particular target that you have selected.

They are quite similar, basically ADV was created based on AD. ADV however is remarkably faster.

There is no general rule for this. The first step would be pre-selecting a relatively large number of compounds (1,000 to 10,000) based on your primary score (the one that is built in your docking engine). Next, more rigorous hit lists should be created based on different scores you have access to (one list per score). Starting from this point, multiple options are open. For example, if you have too many hits based on your initial score and do not have (or do not want) to apply orthogonal techniques to reduce that number, then you might create your final hit list as intersection of all score-based hit lists. If you feel like you need more diversity, then you could use the union of individual lists. Or, if you know something about the performance of each score on your protein target, then each list can be given a different priority based on the confidence level.

I've noticed that the docking using Autodock-vina for metal based systems always returns this error as the parameters for metals in specific are incomplete in the GA algorithm used in Autodock. I would recommend using GOLD if you have a license or for an inexpensive means, pursue HEX docking. They are just as easy if not as quick as Autodock-vina.

Depending upon CPUs, if you use normally 4 cpu it may takes less than 1 min. Also, if size of grid is big, for e.g. 100 x 100 x 100, then it may take 2-5 mins. You need to inspect is the all parameters and protein where you are generating grid is appropriate. I suggest to make one more time preparation of protein and ligand and try for autogrid generation

Few tricks be needed to carryout successfully completion.

1) Update the AD4_parameter.dat according to your necessary metal

2) Update the AD4.1_bound.dat also according to your necessary metal

3) then copy that two files into your installation folder

4) then during grid generation and docking dpf file generation steps, there at set map types option you should mention the required metal atom types and also there is a option named as other option; there u should mention the newly generated parameter file

5) finally the newly generated 2 files should be kept on your docking directory

Finally docking should successfully run.

You would need to perform docking studies with the separate isomers.

You should follow the procedures step by step

before going for AutoGrid, you have to be sure the the grid parameter file "gpf" was written correclty

also, when you go foe AutoGrid, you should correct the program pathname then select the grid parameter file and click "Launch"

Dear collegues,

I have received an answer from Proffessor Sanner (Michel Sanner), who works at the Scripps Research Institute. 

I hope it can  also be useful for you all:

"I have been  working in a version of AutoDock that supports making receptor side  chain flexible and as part of these software developments I wrote the  AGFR software program.

This command line program allows the compute grids (using AutoGrid4) and supports a range of options for automatically positioning of docking

boxes, including using: a known ligand, or a set of residues in the

receptor, a binding pocket identified by our pocket finding method

AutoSite, etc...

The software is not 100% ready for release yet but if you want to give

it a shot you can download the code from

please look at the Use cases on that web page for examples on how to use  the software. (Be aware though that currently the graphical user  interface AGFRgui is broken) but the command like version should be working.

The .trg file contains is a zip file that contains all the maps generated by AutoGrid4 and that can be used for AutoDock4.

So you have to unzip the .trg file and give AutoDock4 the the .map files located in the folder created by unzip.

> unzip myfile.trg

Archive: myfile.trg

inflating myfile/rigidReceptor.C.map

inflating .. "

Thank you all for your help! I really appreciate it!

Huge hugs 

Stellamaris

I agree with Yoshinobu Ishikawa. You can remove the torsional degree of freedom. Also, for rigid body docking, I would recommend ZDock (http://zdock.umassmed.edu/) or ClusPro (https://cluspro.bu.edu/login.php) which are designed for rigid body docking.

If you are using cygwin any way, then better use vi. You need to get used to it. There are some online tutorials.

Dear Gómez-Jeria

I hope this comment finds you in good health and spirit.

For running ADT, you should be following next steps:

1- Make sure that if python 2.5 installed on your PC: you can download it from the following URL:

2- install Autodock tools: you can download it at:

3- install mgltools:

After having finished installation of above tools, you can run ADT. Here, I recommend you to following my current protocol for running it:

1- create a workfolder for your job and tag it based on your favorite name. (e.g. project)

2- running ADT in start menu in windows:

after running you should set its directory: following these steps:

a) open ADT> File> Preferences>set> Startup Directory (in this section you should put on your workfolder path and set it). for example: “C:\Users\project

3- prepare ligand and protein in ".pdb" format. Notice, you must labeled them by "Ligand" and "Protein" keywords.

after having finished these steps you can run ADT: Well! you should do the below ways:

1- open ADT:

File > Read Molecule> Select Protein File (“.pdb” file)

Then:

Edit > Hydrogens >Add>>>>>> Polar Only >OK

Edit > Hydrogens> Merge Non Polar >  Continue (in this step if you see any warning please click on "continue")

then:

Edit > Charges > Add Kolman Charges> Ok

File > Save > Write PDB> >Sort Nodes (Check) > OK > (Overwrite) YES

Well! in the next step you should try prepare the ligand:

Ligand > Input > Open> Select Ligand File (“.pdb” file) > OK

Now repeat above steps and then: (in this section you must add charge to your ligand. So, click on Edit menu and:

Edite> Charges> compute Gasteiger

Ligand > Output > Save as PDBQT

******************************

Now you should be executing AutoGrid4:

For run AutoGrid following the below steps:

1-Grid > Macromole > Choose>  Click (Protein) > Select Molecule > OK > save

2-Grid> Set Map types >Choose Ligand> Click (Ligand) > Select Ligand

3-Grid > GridBox> Set the BOX> File > Close Saving Current

4-Grid > Output > Save GPF> grid.gpf> save

5-Run > Run AutoGrid:

a) Select Program Pathname: ‘autogrid4.exe’ (i.e. C:\Program Files (x86) \The Scripps Research Institute\Autodock\4.2.6)

b) Select Parameter Filename: ‘grid.gpf’ (you should select it based on your workfolder path)

c) Launch!

Notice! in this step you must waiting for ADT response. please don't "dismiss" it!

***************************************************************

After having finished above steps following the below ways:

Run ADT:

1)Docking > Macromolecule > Set Rigid filename> Select ‘Protein.pdbqt’ > Open

2-Docking > Ligand > Choose> Click ‘Ligand’ > Select Ligand> Accept

3-Docking > Search Parameters > Genetic Algorithm> Accept

4-Docking > Output > Lamarckian GA> Save file as ‘dock.dpf’

5-Run > Run AutoDock 

A) Select Program Pathname: ‘autodock4.exe’ (C:\Program Files (x86)\The Scripps Research Institute\Autodock\4.2.6)

B) Select Parameter Filename: ‘dock.dpf’ (Based on you workfolder path)

C) Launch!

Please wait for finishing and don't dismiss it!!

***********************************************************

Docking result analysis:

1-Analyze > Docking > Open> Select ‘dock.dlg’ > Open >Assign Ligand New Name > OK

2-Analyze > Macromolecule > Choose> Click ‘Protein’ > Select Macromolecule

3- Analyze > Conformations> Play, Ranked By Energy > Click on the ‘&’ Button

4-Set Play Options >Check ‘Build H-Bonds’> View the hydrogen bonds formed > Check ‘Show Info’> View the Interaction Energy > Build Current Write Complex> Save as ‘Result.pdb’ ” Save....

Now you can see all of your docking results!

This current protocol can help you for running ADT. I hope it was useful for you. Please do not hesitate to contact me if you have any further questions. Otherwise, I hope that we can work together successfully again another time.

All the best,

Hassan

Dear   Selvaraj

I hope this comment finds you in good health and spirit.

For running ADT, you should be following next steps:

1- Make sure that if python 2.5 installed on your PC: you can download it from the following URL:

2- install Autodock tools: you can download it at:

3- install mgltools:

After having finished installation of above tools, you can run ADT. Here, I recommend you to following my current protocol for running it:

1- create a workfolder for your job and tag it based on your favorite name. (e.g. project)

2- running ADT in start menu in windows:

after running you should set its directory: following these steps:

a) open ADT> File> Preferences>set> Startup Directory (in this section you should put on your workfolder path and set it). for example: “C:\Users\project

3- prepare ligand and protein in ".pdb" format. Notice, you must labeled them by "Ligand" and "Protein" keywords.

after having finished these steps you can run ADT: Well! you should do the below ways:

1- open ADT:

File > Read Molecule> Select Protein File (“.pdb” file)

Then:

Edit > Hydrogens >Add>>>>>> Polar Only >OK

Edit > Hydrogens> Merge Non Polar >  Continue (in this step if you see any warning please click on "continue")

then:

Edit > Charges > Add Kolman Charges> Ok

File > Save > Write PDB> >Sort Nodes (Check) > OK > (Overwrite) YES

Well! in the next step you should try prepare the ligand:

Ligand > Input > Open> Select Ligand File (“.pdb” file) > OK

Now repeat above steps and then: (in this section you must add charge to your ligand. So, click on Edit menu and:

Edite> Charges> compute Gasteiger

Ligand > Output > Save as PDBQT

******************************

Now you should be executing AutoGrid4:

For run AutoGrid following the below steps:

1-Grid > Macromole > Choose>  Click (Protein) > Select Molecule > OK > save

2-Grid> Set Map types >Choose Ligand> Click (Ligand) > Select Ligand

3-Grid > GridBox> Set the BOX> File > Close Saving Current

4-Grid > Output > Save GPF> grid.gpf> save

5-Run > Run AutoGrid:

a) Select Program Pathname: ‘autogrid4.exe’ (i.e. C:\Program Files (x86) \The Scripps Research Institute\Autodock\4.2.6)

b) Select Parameter Filename: ‘grid.gpf’ (you should select it based on your workfolder path)

c) Launch!

Notice! in this step you must waiting for ADT response. please don't "dismiss" it!

***************************************************************

After having finished above steps following the below ways:

Run ADT:

1)Docking > Macromolecule > Set Rigid filename> Select ‘Protein.pdbqt’ > Open

2-Docking > Ligand > Choose> Click ‘Ligand’ > Select Ligand> Accept

3-Docking > Search Parameters > Genetic Algorithm> Accept

4-Docking > Output > Lamarckian GA> Save file as ‘dock.dpf’

5-Run > Run AutoDock 

A) Select Program Pathname: ‘autodock4.exe’ (C:\Program Files (x86)\The Scripps Research Institute\Autodock\4.2.6)

B) Select Parameter Filename: ‘dock.dpf’ (Based on you workfolder path)

C) Launch!

Please wait for finishing and don't dismiss it!!

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Docking result analysis:

1-Analyze > Docking > Open> Select ‘dock.dlg’ > Open >Assign Ligand New Name > OK

2-Analyze > Macromolecule > Choose> Click ‘Protein’ > Select Macromolecule

3- Analyze > Conformations> Play, Ranked By Energy > Click on the ‘&’ Button

4-Set Play Options >Check ‘Build H-Bonds’> View the hydrogen bonds formed > Check ‘Show Info’> View the Interaction Energy > Build Current Write Complex> Save as ‘Result.pdb’ ” Save....

Now you can see all of your docking results!

This current protocol can help you for running ADT. I hope it was useful for you. Please do not hesitate to contact me if you have any further questions. Otherwise, I hope that we can work together successfully again another time.

All the best,

Hassan

Dear  Badihi

I hope this comment finds you in good health and spirit.

For running ADT, you should be following next steps:

1- Make sure that if python 2.5 installed on your PC: you can download it from the following URL:

2- install Autodock tools: you can download it at:

3- install mgltools:

After having finished installation of above tools, you can run ADT. Here, I recommend you to following my current protocol for running it:

1- create a workfolder for your job and tag it based on your favorite name. (e.g. project)

2- running ADT in start menu in windows:

after running you should set its directory: following these steps:

a) open ADT> File> Preferences>set> Startup Directory (in this section you should put on your workfolder path and set it). for example: “C:\Users\project

3- prepare ligand and protein in ".pdb" format. Notice, you must labeled them by "Ligand" and "Protein" keywords.

after having finished these steps you can run ADT: Well! you should do the below ways:

1- open ADT:

File > Read Molecule> Select Protein File (“.pdb” file)

Then:

Edit > Hydrogens >Add>>>>>> Polar Only >OK

Edit > Hydrogens> Merge Non Polar >  Continue (in this step if you see any warning please click on "continue")

then:

Edit > Charges > Add Kolman Charges> Ok

File > Save > Write PDB> >Sort Nodes (Check) > OK > (Overwrite) YES

Well! in the next step you should try prepare the ligand:

Ligand > Input > Open> Select Ligand File (“.pdb” file) > OK

Now repeat above steps and then: (in this section you must add charge to your ligand. So, click on Edit menu and:

Edite> Charges> compute Gasteiger

Ligand > Output > Save as PDBQT

******************************

Now you should be executing AutoGrid4:

For run AutoGrid following the below steps:

1-Grid > Macromole > Choose>  Click (Protein) > Select Molecule > OK > save

2-Grid> Set Map types >Choose Ligand> Click (Ligand) > Select Ligand

3-Grid > GridBox> Set the BOX> File > Close Saving Current

4-Grid > Output > Save GPF> grid.gpf> save

5-Run > Run AutoGrid:

a) Select Program Pathname: ‘autogrid4.exe’ (i.e. C:\Program Files (x86) \The Scripps Research Institute\Autodock\4.2.6)

b) Select Parameter Filename: ‘grid.gpf’ (you should select it based on your workfolder path)

c) Launch!

Notice! in this step you must waiting for ADT response. please don't "dismiss" it!

***************************************************************

After having finished above steps following the below ways:

Run ADT:

1)Docking > Macromolecule > Set Rigid filename> Select ‘Protein.pdbqt’ > Open

2-Docking > Ligand > Choose> Click ‘Ligand’ > Select Ligand> Accept

3-Docking > Search Parameters > Genetic Algorithm> Accept

4-Docking > Output > Lamarckian GA> Save file as ‘dock.dpf’

5-Run > Run AutoDock 

A) Select Program Pathname: ‘autodock4.exe’ (C:\Program Files (x86)\The Scripps Research Institute\Autodock\4.2.6)

B) Select Parameter Filename: ‘dock.dpf’ (Based on you workfolder path)

C) Launch!