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I performed molecular docking using auto dock tools, specific protein was docked with different ligands. During the preparation of ligand.pdbqt files, I should select the same number of active torsions for these ligands. When I open ligand.pdb file, the program tell me about the number of active torsions for this ligand which differ from one ligand to another. Actually, I fixed the number of active torsions for all ligands =4. I do not know if this right or not. Please, can any one help in this issue?
Thanks in advance.
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Thank you Mahla Mehrparvar for your recommendations.
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I have performed simulation of protein. Now, I wish to do docking of this simulated protein with my ligand. I have converted the .xtc file of protein to .pdb. As I am trying to open my protein in autodock it is showing traceback error. How should I solve this?
The size of the pdb file of my protein is 417 mb.
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you need to clean your file preferably extracting the protein chain only. which should be within 1 MB.. You might be having solvent and membrane in your pdb.
If the problem still persists your peptide backbone could have an issue but that is unlikely as it's already accepted and simulated.. Which simulation software do you use?
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After docking in CDOCKER how to save the best pose for MD Simulation in Desmond? I saved the protein and ligand molecule in pdb format seperately. After that I paste the ligand coordinate file at the end of the protein coordinate file. When I open the complex in maestro the double bond of the rings of tge ligand did not show. How should I fix the problem? Please help me out
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Hello
You should save your complex in sdf, mae, or mol format in .pdb format bond conjugation does not show in maestro.
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I have 3 different docked structures of 4 proteins (1 protein docked with 3 variants of another protein) with 3 different energy values.
So, can anyone suggest any methods with which I can find the probable cause of those three different interactions?
Thank you in advance!!
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Jameel M. Abduljalil Thank you a lot
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I did protein protein docking through clus Pro then I am trying to see the interaction through ligplot but after putting the docking results it's not showing anything its showing "no interaction". But my results came with a good lower energy score.
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@Prasanth Kumar problem solved, thank you so much.
Solution:
Open the PDB file on PyMOL and follow these instructions to add/alter the chain identifier:
select the chain for which you wish to add/alter the chain id
*make sure that the selecting state (on the bottom right side) is on chains
type the command: alter (sele),chain='A'
*This will alter the chain id to A, if you want another id change the command accordingly
type the command: sort
Open the file menu, click on Save Molecule, select the option 'sele' and save (give a new file name)
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the molecular Docking simulation does not generate an IC50 value, it gives calculated inhibition constant (Ki) values! Unless you know a method and equation to make this conversion, you cannot use the Docking value as an IC50 value.
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Kd is binding constant. Make Kd the subject https://en.m.wikipedia.org/wiki/Binding_constant
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Hello everyone,
I need your help please
I am docking a mixed complex with a coordinence of 6 using autodock vina.
Once the calculation is done, I can't visualize the interactions because my complex is decomposed. I even used other programs like ligplot and protein plus server. They gave me the interractions of one of the ligands with the protein but not the whole complex. Knowing that the complex was optimized by DFT and saved in .pdb to be used for docking.
Thank you.
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Hello
I agree with Udaya Kumar and suggest you try using Discovery Studio and choosing residue to see the interactions.
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I am looking for residue number or insertion code for covalent docking.
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Google your protein name [protein name in PDB] to find it.
(All codes relating to your protein in PDB will appear.)
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I want to dock Nortriptyline into hDAT model as the authors of did.
I prepared the structures of ligand and protein as the article said. However nortriptyline posed in different way in my case.
Could it be because I'm using a different program for ligand optimization (Avogadro instead of MAESTRO)?
Could the new version of Vina give another result?
Or I did mistakes when pdbqt-files were being prepared?
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Because you don't know what configuration was used for ligand optimization, you can't exactly replicate the same pose as in the literature.
Optimization with different tools will result in different docking poses, and different versions of the same tool will also influence the binding pose as new features that contribute to binding pose prediction are added.
If it docks smoothly, it usually means you didn't make any mistakes when preparing the files.
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Hi everyone,
as the newer version of Autodock Vina 1.2 version released last year ( ), I was excited to use the newer version of this docking app. Although the authors did not declare any change in the scoring function between Vina 1.2 and 1.1.2 in the latter article, I found that there was a difference between docking pose retrieved from Vina 1.2 to Vina 1.1.2 version using the same configuration parameters (I am doing blind docking).
So I am asking for if there is any difference between these two scoring functions? And which is more reliable to conduct a new in silico research? Thank you very much.
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Waseem Ahmad Ansari thank you for answering, however I am trying to reproduce a result from previously published study using Vina 1.1.2. Although I have put the high exhaustiveness (128), it could not reproduce the result by 1.2.
So it just my question if which one is more reliable because the authors didn't declare any difference between two scoring functions :(
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Hello, please help me with a docking problem in HEX 8.0. I try to dock ethidium bromide into the structure of a B-DNA DODECAMER (1BNA) and I hope to find an intercalation mode of binding as it is a known DNA intercalator but the docking simulation shows binding into the minor groove of DNA. After I download the pdb structure of DNA I remove the water molecules and save it as pdb format. I optimize the structure of Ethidium bromide in Avogadro 1.01 and then open the receptor (DNA) and the ligand (Ethidium Bromide) in HEX 8.0 and do the docking with the automatic settings (Correlation Type - Shape Only). Where am I wrong? Thank you for your time!
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Excellent !
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Hlo everyone
I want to know that on hat grounds or how we should select different ligands for our protein from different databases and how to validate it whether the selected ligands are correct or not.
Please help me out.
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I agree to Prasad Dhiwar
You can just draw or upload the structure to Zinc database and perform similarity checks. It will give an array of molecules which can be downloaded in desired format.
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I have a protein with metal atom- Nickel in the active pocket. Also ligand will be stabilized better after making interactions with Nickel atom.
Issues-
1.After protein preparation, charge of nickel atom is converted to zero.
2. Docking scores of ligands are showing positive values
I am familiar about the process if the ligands have metals. Have referred few questions and answers posted by other researchers. Any guidance please..
Thanks in advance
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Jobin Thomas Thank you for suggestion. I have tried adding parameters of Nickel in dat file. Still the docking score was positive value.
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Hi everyone, I'm currently working on an autodock4 and I've received those warning in my running process. I don't know how to fix or how it affects to my final results. Attached below are my dpf file and cmd warning.
Thanks for your advices.
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I hope you doing well
This error is showing in .dpf file. So you should generate again .dpf file or check notepad file of .dpf and change the terms which will be shown in attach pic.
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I am docking a ligand in a protein scaffold using PyRx but after docking, I need its coordinates. It will be very helpful if I could know how to get the coordinates of the docked structure.
- Thank You
Arindam
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Use BIOVIA Discovery Studio
Load the complex and select the ligand
Then under "Receptor-Ligand Interactions" section click on "Define Site" (Click "From current selection")
This will form a bubble in the ligand site
Select the bubble (will appear yellow in colour)
Right click on the bubble and and click Attributes of SBD_Site_Sphere
It will open a window showing your coordinates
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I have performed protein ligand 10ns md simulation on my docked complex in gromacs but when I visualize xtc file in vmd and after saving it in pdb, in pymol I see the ligand is a bit away from protein and outside protein, and also long lines like structures with protein.
What can be reason of these? Does this means there are problems with simulation but how it can be validated?
Please help me in this matter.
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dear Mr Suparna Ghosh , I've do your recommendation/solution but it is still cannot fix the problem, do you have any solution? may i know the other solution? thank you in advance
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Hi all,
I'm a master student working with computational molecular fragmentation and docking.
I did a virtual screening using autodock vina of some thousends of molecules, and I'm wondering if there's a solution to fragment the molecules based on the interactions observed on the docking poses. In the end I want obtain the smiles of the fragment, the AA the fragment is interacting and the type of interaction.
Is there any methods to do this?
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Hi Nikolaos Kourkoumelis, thanks for your answer. Indeed, unfortunately I didn't find the code
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I want a technique through which I can dock replication proteins of a bacteria to its DNA to find the residues where they bind with each other.
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I was referring to in silico docking. Thanks for the advice about using EMSA as I did not have the minimal binding site for my protein sequence, this would allow me to use HDock for my purposes.
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Hi all,
I'm a master student working with computational molecular fragmentation and docking.
I did a virtual screening using autodock vina of some thousends of molecules, and I'm wondering if there's a solution to fragment the molecules based on the interactions observed on the docking poses. In the end I want obtain the smiles of the fragment, the AA the fragment is interacting and the type of interaction.
Is there any methods to do this?
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hi Gautam Bhardwaj, thanks for yout answer. I used qsar models too for the prediction of activity, using fingerprints and molecular descriptors. But the idea here is really to have the fragments, the AA they are interacting and the type of interaction. The methods of fragmentation I know are only smarts-based or rules-based, and I'm looking for a structure-based methods
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I am currently docking a few millions of compounds through a Cluster using VirtualFlow. However, I currently need a list of interacting residues from the docking for all of the docking done. I am able to find the interacting residues using AutoDock Tools or Discovery Studio manually, but I won't be able to manually obtain the residues of the millions of compounds. Would there be an automated way to obtain a list of all interacting compounds from all the docking?
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Hi,
from AutoDockTools I don't think it would be possible, but you can try BINANA (https://git.durrantlab.pitt.edu/jdurrant/binana).
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Based on PubChem calculation, the ligand structure only possess 1 rotational bond (TORSDOF). However, the ligand structure that came out from DFT optimization has been calculated differently by AutoDock with 5 TORSDOF. Interestingly, from 5 of them, there is not any single bond that the same one as what PubChem found.
So, should I directly just use DFT-optimized ligand structure OR I change the TORSDOF number and rewrite its structure file (.pdbqt), then use the rewrited one?
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Thank you for the nice answer, Shamasoddin.
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After Autodock docking, I tried preset-ligand site for interaction in Protein-ligand.
But I cannot find any interaction.
Is that mean there is no interaction between protein-ligand?
There is log file below for docking
WARNING: The search space volume > 27000 Angstrom^3 (See FAQ)
Output will be DB02192_out.pdbqt
Detected 8 CPUs
Reading input ... done.
Setting up the scoring function ... done.
Analyzing the binding site ... done.
Using random seed: -617173320
Performing search ... done.
Refining results ... done.
mode | affinity | dist from best mode
| (kcal/mol) | rmsd l.b.| rmsd u.b.
-----+------------+----------+----------
1 -4.4 0.000 0.000
2 -3.8 29.437 30.282
3 -3.7 27.939 29.198
4 -3.6 45.368 45.805
5 -3.5 27.753 28.864
6 -3.4 14.464 16.293
7 -3.3 31.134 32.031
8 -3.3 1.472 2.559
9 -3.2 31.325 32.445
Writing output ... done.
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Good Day
After loading your complex, you may follow these orders in Pymol (right-click on the ligand - action - find - polar contacts - to any atoms), If you still can't see the interaction, you may use ligplot++ or discovery studio. If you still can't find the interaction, it's best to redock because your outputs are a little bit high, ( good docking ) and should be low-value mean (high negative value).
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I have list smiles of active set target retrieved from bindingdb database, and i want to generate properties matched decoy structures to perform retrospective docking validation. I have tried dud-e server (http://dude.docking.org/) and Tldr's a Ligand Discovery Resource (tldr.docking.org), unfortunately give no result. Is there any online server to build decoy structures?
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Dear Saipul,
DUD-E is the most commonly used tool for decoy generation. I also tried RADER and Decoy Finder some years ago. Unfortunately, RADER is not working anymore. Decoy Finder 2.0 (https://www.macinchem.org/blog/files/82be9fdea59e8e6dd18b7ee06bc027d9-1718.php) is still available, but from my experience, it works too slowly (it can take many hours, so one has to keep the computer turned on until Decoy Finder finishes the job).
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Two different proteins which are well known for forming a hexamer ring by making electrostatic interaction among its heterodimers, reported in yeast and the structure is also available in PDB. I am looking for the same two proteins in but in an eukaryotic parasite. To do so, I first used alpha-fold to generate homology models of the monomers of these two proteins. However, these proteins have a tendency to form dimer and then a hexameric ring. I was wondering if a server is available that can do oligomerization docking. Please suggest. I have used Lzerd software but I don't see any satisfactory result, it doesn't form hexameric structure in the output model but fetched an arbitrary complex with no meaning. Your suggestion will be much appreciated and well acknowledged.
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If your template structure (of yeast) has the arrangement you want (a ring of heterodimers), then you can use the CIF file (obtained from Protein Data Bank) in alphafold to build the complex structure.
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I have performed molecular docking and in the interaction diagram of the protein-phytochemical complex, only hydrophobic bonds are there, no hydrogen bonds are involved with any residues of the protein.
I had selected this one as one of the final compound after virtual screening. That compound behaved well in MD simulation considering low RMSD, RMSF values. Binding affinity was also higher than the control drug.
Now can I propose that compound as my potential findings for the paper??
Please help. Thanks a lot.
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The main problem with ligands that only interact through hydrophobic contacts is that these tend to show very low specificity - you may want to look at the possibility to introduce more specific interaction in further development of the lead. While hydrophobic interactions provide the majority of the interaction energy, hydrogen bonds and charge interactions provide specificity.
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I recently made some dockings with certain substances and obtained negative values of "VINA Score" but I don't know how to interpret it.
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The more negative number is your answer.
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I have a library of covalent compounds, and I want to run covalent docking for them using Autodock 4. Is there any possible way where I can run multiple compounds at once, like is it possible to use all ligands in a single file, or a certain command that can run all of them at once?
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Hello everyone,
I tried to dock a ligand to a molecule using AutoDock software with a blind docking method. My ligand is an under-investigated small-drug molecule and the protein interactions of the ligand is not known. From my docking results the binding energy for the molecules I investigated was found as -5.78, however there was no hydrogen bonds formed between these molecules. Can I assume that these molecules are docked or how can I check the reason why hydrogen bonds weren't formed?
Additionally, is there any way anyone can recommend to screen the proteins interacted with a ligand whose proteins interactions weren't studied?
Sorry for the inconvenience,
Thanks in advance.
Mervenur
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Hi mervenur
Please paste the coordination of the best pose of docked molecule to the pdb structure of protein (without water molecules) and open it BIOVA discovey studio Visualizer. It can be downloaded from following address:
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Are there certain precautions while preparing zinc fingers - containing proteins for MOLECULAR DYNAMICS SIMULATION?
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Hello,
As stated, simulation with metal centers can become a difficult endeavour. It all depends on your ultimate goal.
A rather "simple" approach is the use of positional restraints. Other methods use dummy atoms or additional parameters to improve the description (either geometric or electronic, but not both). A comprehensive description would also need of QM/MM methods.
I'm not a frequent user of GROMACS, but the AMBER documentation has several tutorials you could use as a starting point to gain some insight on the possibilities and choose based on your intended purpose for the simulation.
Hope this helps,
Regards
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I use the free version of PyRx. It is bugging me for quite some time that every time I try to dock a specific ligand with a specific protein, the binding affinity differs. Sometimes, the difference is too much. For your convenience, I am giving an overall idea of how I do that.
1) At first, I prepare the ligand and protein and minimize their energies with different softwares.
2) Then I dock them in PyRx.
I follow the the procedure every time. However, the results are not the same. Can anyone help me out?
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1- Minimize the energy of the ligand using Open Babel in the PyRx software
2. It's better to determine the specific amino acid you need, then make the grid box depending on that for accurate results, better than docking randomly.
3- You can try that many times until finding the highest negative charge with a good dock, then you can examine the interaction using BIOVIA Discovery Studio Visualizer.
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Hy everyone
I am running MD simulations in AMBER software for docked ligand and protein but I am getting bit confused for while running few of them whether to use them or not.
So anyone can give me list of commands of running md in amber which are error free nd directly can be used.
Thank you
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Hi, as per your requirement, you should follow this tutorial:
once you are comfortable using Amber, you should look into the details of various settings to suit your use case.
However, I recommend you to follow LEAP/tleap tutorial/introduction first to get accustom with the Amber functioning/utilization.
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I'd want to dock biotin with an aptamer's 3'/5' end. I'm not sure how I'd go about doing it precisely on that end. When I use the HDOCK web server to dock between the aptamer and the biotin, they bond the center of the aptamer. So, what's the best way for me to address this issue?
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I think you need to use some kind of positional restraint. E.g., Schrodinger Glide allows setting the maximal allowed distance between specific atoms of ligand and receptor, thus one can force the ligand to dock in a specific orientation. Probably, GOLD, FlexX, and many other tools have this option as well.
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In need of SYBYL-X or Gaussian software for ligand-ligand docking. Anybody having the same or having any lead regarding these, please do the needful, I shall be highly grateful to you.
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Here's a tool for studying drug-drug interactions:
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i would like to learn drug design specially docking but i dont know how to start since i have no previous experience in this field as being a polymer chemist
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I too am new to molecular docking but have found the following videos very useful:
https://youtu.be/EI7ojGoLLUk - basic 5 min intro to docking
https://youtu.be/k6tqCeDIwEk - full introduction to docking with Autodock
https://youtu.be/pt4F6hnDvBk - general interest, shows a couple of applications of docking
https://youtu.be/l-_6tbk_ey0 - intercalation of proflavine into DNA
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when I docked peptide and protein in the patch dock, it gives me ten best structures. should I work with all these ten structures?
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You can choose several poses that appear by considering the ACE value. You can discuss the quality of the interaction based on the obtained ACE value.
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I am performing protein-ligand complex MD simulation after docking. The ligand stays intact intially but is found far away in md.gro file from protein during the md run of 100ns.
Kindly help me with this.
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Since the protein is rigid in most of the docking softwares, I guess this is normal when you start MD due to the potential energy change. You can apply a constraint on ligand-protein COM distance and then you can slowly remove it.
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Hy everyone
I was running the md simulations using AMBER software. While running the commands for protein after ligand commands do we have to use the docked protein in the command 'complex = loadpdb 1ua7_noh.pdb' or just the protein in the pdb file.
Thanks and Regards
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aus "1ua7_pyr.pdb"
...
ATOM 4071 OXT ASP A 425 -6.429 2.945 49.965 1.00 53.85 O
ATOM 4072 HN ASP A 425 -6.232 4.618 53.867 1.00 53.00 H
TER 4073 ASP A 425
HETATM 4074 N UNK N 1 -11.184 37.228 27.319 0.00 0.00 N
HETATM 4075 C UNK N 1 -11.023 38.325 26.559 0.00 0.00 C
HETATM 4076 C UNK N 1 -12.297 36.603 26.893 0.00 0.00 C
HETATM 4077 C UNK N 1 -12.044 38.406 25.634 0.00 0.00 C
HETATM 4078 C UNK N 1 -12.856 37.307 25.847 0.00 0.00 C
HETATM 4079 H UNK N 1 -10.562 36.918 28.095 0.00 0.00 H
TER 4080 UNK N 1
...
aus "pyr_h.pdb":
REMARK BIOVIA PDB file
REMARK Created: 2022-06-22T01:03:24Z
HETATM 1 N UNK N 1 -11.184 37.228 27.319 0.00 0.00 N
HETATM 2 C UNK N 1 -11.023 38.325 26.559 0.00 0.00 C
HETATM 3 C UNK N 1 -12.297 36.603 26.893 0.00 0.00 C
HETATM 4 C UNK N 1 -12.044 38.406 25.634 0.00 0.00 C
HETATM 5 C UNK N 1 -12.856 37.307 25.847 0.00 0.00 C
HETATM 6 H UNK N 1 -10.562 36.918 28.095 0.00 0.00 H
HETATM 7 HC UNK N 1 -10.216 39.036 26.657 0.00 0.00 H
HETATM 8 HC1 UNK N 1 -12.693 35.688 27.308 0.00 0.00 H
HETATM 9 HC2 UNK N 1 -12.182 39.176 24.890 0.00 0.00 H
HETATM 10 HC3 UNK N 1 -13.752 37.050 25.301 0.00 0.00 H
END
No two atoms in one residues can have the same atom names, therefore the different C atoms need to be differentiated, e.g as C1, C2, C3, C4
In addition, the pyrrole residue named "UNK" cannot be found in the set of FF libraries you loaded in LEaP - if a description for pyrrole is contained in these libraries, you need to make sure that residue name, atom names and atom orders match- if not you will
have to develop a new library for this new residue/the corresponding
molecular fragment. For that you could use R.E.D. or R.E.D. Server;
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I was using autodock for covalent docking, and some of my compounds had very high estimated energies (e.g. +110 kcal/mol, etc.). Are these results true, or is there some error with the docking parameters?
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Make sure that the docking protocol is validated
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My ligand contain fluorine atom in it, but when I am trying to run docking with protein (PDB id: 2c65) this problem is occurring. Please if anyone can solve this problem it would be very helpful.
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The grid maps to be generated are defined in the grid parameter file (GPF).
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Hi guys, iam screening around 1000 compounds in batches using Pyrx. I wanted to know is it possible to in pyrx to load your original grid configuration without manual moving the grid box. Im docking several batches of compounds using the same grid configuration. Please assist, thank you
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Hey Jonathan T Bvunzawabaya did you find out if it's possible to add the configure.txt file on PyRx?
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Recently I have been involved in performing both precision and global docking using the leishmania mexicana arginase (PDB ID: 4IU1). None of my ligands do not go to active site of the protein after precision and global docking. It kind of weird to me since structurally related compounds have been reported to interact with the active site. I was thinking maybe autodock vina may not dock metalloenzymes.
Please I need a way out.
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Thank you Ibrahim
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actually i want to do virtual screening of aptamers and proteins in such a way that i placed aptamers as a ligand and protein as a receptor and want to do docking and then further virtual screening my aptamers are DNA based but the problem is this i couldnot find any good software for this. i tried autodock vina iGEMDOCK, pyrx and many others like this but it didnot work. can anyone please suggest software for this ?
thanks in advance.
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u can try HDOCK server..
HDOCK: a web server for protein–protein and protein–DNA/RNA docking based on a hybrid strategy
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While uploading a docked complex (.pdb) onto the PDBsum generation, it shows the following -
Uploaded file contains invalid residue names. Please check that your PDB file conforms to correct PDB conventions.
thanks in advance
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Hello Muhammad Adnan Ali,
According to your arrised question, you have wrong file file format for input of PDBSUM (it will only take .pdb extension file for generating any output files). For your convience i have attached the .pdb file below in this comment.
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How much chemplp fitness score should be considered in protein-ligand virtual screening using GOLD software.
I have a library of molecules that are already screened using Autodock vina. Want to verify the vina docking results by GOLD docking.
Any suggestion or input would be highly appreciated.
#Golddocking
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Dear Muhammad, do you have any datasets to test your screening protocols on (e.g., known actives and decoys)? This way you can estimate how well the Chemplp fitness score (and Vina scoring function) ranks the actives vs. decoys to decide how much can you rely on GOLD & Vina for your specific target.
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Molecular docking and Molecular mechanics Poisson Boltzmann Surface Area (MMPBSA)
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Thanks Mario E. Valdés-Tresanco . Looking forward to it !
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I receive this error when I try to do virtual screening with vina for flexible docking. does anybody know what should I do?
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Flexible docking is when some residues in the interacting bodies (receptor and ligand) are kept flexible, leaving the rest of the part rigid. Please describe how you prepare your flexible residues and ligand atoms? Can you share a receptor coordinate file that includes all hydrogen atoms? Then, I can help you to solve this problem.
Regards
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I was trying to run a command for covalent docking on autodock using preparecovalent.py on python 3.10.4, and I get this error:
Traceback (most recent call last): File "/home/ahmed/Downloads/adCovalentDockResidue/adcovalent/prepareCovalent.py", line 37, in ob = pybel.ob AttributeError: module 'pybel' has no attribute 'ob'
I can't find any ob attributes in my files.
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Since you can't find any ob attributes in your python script file, its likely that openbabel (ob) isn't/properly installed on your system. Try installing openbabel from source and try running again.
If error persists, i will suggest you use any advanced software (MOE or Schrodinger) for your covalent docking for they are best suitable to achieve this course compared to using a conventional docking tool like autodock.
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Hi ,
I am facing some problems in my ligand-protein (docked complex) simulation.
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Program: gmx grompp, version 2019.5
Source file: src\gromacs\gmxpreprocess\grompp.cpp (line 610)
Fatal error:
number of coordinates in coordinate file (complex_solv.gro, 61208)
does not match topology (topol.top, 61207)
For more information and tips for troubleshooting, please check the GROMACS
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I already searched on the internet and tried to figure it out by myself but couldn't. I am attaching the topology and gromacs files too.
Please help me figure this out if anyone can. Thanks
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have you used -p topol.top option in your command??
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I have been using CLUSPro 2.0 for protein-protein docking, but it does not take the metal ion into consideration because it selectively takes the protein chain. In contrast, HADDOCK considers the metal ion but i can only able to fed the monomoric protein bound with ion to the monomeric target receptors. How can i rectify the issue.Is it feasible to consider the dimeric target protein as a single entity, if so HOW???
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Well, you can trick most programs into accepting a multi-chain protein (homo- or hetero-oligomer) as a single chain protein by first making sure that each amino acid has an unique residue number and then setting all to the same chain ID:
e.g. for a dimer with 100 residues in each chain (chain A and B), set the residue numbers to 1-100 for chain A, 101-200 for chain B, then set the chain ID to A for all residues.
You can do this using the "alter" command in PyMOL https://pymolwiki.org/index.php?title=Alter&redirect=no
alter (chain B), resi=str(int(resi)+100)
alter (chain B), chain="A"
The only problem with this approach is that the C-term of chain A and the N-term of chain B will not be treated as proper charged termini, but rather as a chain break due to unresolved residues. Therefore in the immediate vicinity of these termini, the electrostatics will be off, and these termini will not be able to form the appropriate hydrogen bonds, therefore docking solutions involving@ this region will be suspect.
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i am trying to perform docking using Autodock Vina then do a molecular dynamics simulation for the complexes. but the steps includes adding gasteiger charges to the molecules which is different from the partial charges from CGenFF. so if i want to perform an MD simulation using CHARMM36 FF, is it correct to modify the partial charges obtained from the preparation step of molecules (adding gasteiger charges) to be the charges obtained from CGenFF?
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Abdo A Elfiky Zhaoxi Sun Thank you for your help
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I'm comparing my top1 ligand in docking and my reference ligand. My reference ligand has more strong interactions than my top1 ligand but my reference ligand has a less negative binding energy than my top1 ligand.
Theoretically it should be the opposite right because complex with stronger interactions should have more negative binding energy. But the actual results are different.
What is the explanation for this? Is there something that I'm missing out to study?
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Check the docking score on the basis of that you can conclude the strong binding interaction between ligand and refrence.
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I need to dock a small molecule in the form of a stable salt to a macromolecule using AutoDock4. I completed the docking simulation and during analysis of the docking results, I found that the ligand has been dissociated and only a part of it is bound to the activesite of the macromolecule. How reliable is this docking using AutoDock4. Can the software handle stable salt-like ligands? Can the software correctly judge as to which part of the ligand should dissociate and bind to the macromolecule?There is not experimental evidence on this work.
Any help in this regard will be highly appreciated. Thank You
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"How reliable is this docking using AutoDock4." - It's completely unreliable.
"Can the software handle stable salt-like ligands?" - No, it can't, you need to have covalent bonds between all atoms. Otherwise just dock these two ionic parts separately.
"Can the software correctly judge as to which part of the ligand should dissociate and bind to the macromolecule?" - No, this is not the goal of this software.
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In PYRx for docking a mutated protein while trying to convert protein as macromolecule, I am finding error so that I cannot continue with docking. Kindly may I know how to resolve this issue. Thanks in anticipation.
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Energy minimize the protein. This will do......
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Hi, I am a beginner in bioinformatics. I had determine the xyz coordinate of active site for my protein of interest, the coordinate was [69.37, 61.754, 58.738].
But when I repeat the same procedure on the same protein, the xyz coordinate has been changed to [ -9.604, 0.186, -20.754], does anyone know what happened and how to fix this?
This happened when I do docking with Autodock as well
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Hi Sammy Zhen , I think the coordinate that you've obtained from journal is an altered coordinate. It means that, maybe the author moved the protein when viewing and saved it in a new coordinate. Thus, its center coordinate has been changed.
In my opinion, if you're doing specific docking, determine the active residues first and set up a grid box that can cover whole active residues.
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Hi,
I wonder if anyone knows how to create ensembles using the pdb-tools (https://wenmr.science.uu.nl/pdbtools/reference)? The protein-protein docking have been completed by InterEvDock2 where I set different constraints and did several docking runs. Because the InterEvDock2 only performs rigid docking, I would like to normalize the score of different runs using pdb-tools. For each docking run, I need to create an ensemble with a few best docking poses. However, I don't know how to implement it in pdb-tools (what specific pipeline needs to be loaded).
Any feedback is welcome. Thanks.
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Ensemble docking allow to dock a single ligand or a ligand library against multiple conformations of a single receptor.
Now, imagine we have a group of proteins which are functionally conserved and share similar ligand/s. Moreover, they are highly similar in the structures (Identity rate in AA level is more than 90%) and almost a perfect superimposition of 3D structure can be made by different tools.
Docking analysis was performed for each protein solely and as expected the binding pocket and residues are similar.
Now here is the question: Can we perform Ensembled docking for this situation?
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Usually "ensemble" means "configurational ensemble," i.e., a collection of structures of a single system, with the structures differing only in atomic coordinates. But technically, yes, one can make an ensemble of different systems and dock into them -- if the structures (and pharmacophore features) align well . . .
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I have to perform PCA as a part of my results and analysis of protein-ligand complex docking using GROMACS 2018.8. How shall I perform PCA and interpret the results for the same?
Any insights will be highly appreciated.
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gmx trjconv -f md_0_1.xtc -s md_0_1.tpr -o md_protein.xtc -center -ur compact -pbc mol
gmx trjconv -f md_0_1.xtc -s md_0_1.tpr -o md_protein.pdb -center -ur compact -pbc mol -dump 0
gmx convert-tpr -s md_0_1.tpr -o md_protein.tpr
gmx covar -f md_0_1_noPBC.xtc -s md_0_1.tpr -v eigenvec.trr
gmx anaeig -v eigenvec.trr -f md_0_1_noPBC.xtc -eig eigenval.xvg -s md_protein.pdb -first 1 -last 2 -2d
gmx anaeig -v eigenvec.trr -f md_0_1_noPBC.xtc -eig eigenval.xvg -s md_protein.pdb -first 1 -last 2 -2d 2dproj_ev_1_2.xvg
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I want to calculate rerank score for my docking complex. How I can do it? Could anyone please give some easy references or procedures to understand the calculation?
Thanks.
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Which tool you have used for docking. If you use the docking program like GOLD/DS/AutoDock you can rescore the function during your docking run. However, if you are a single scoring function then you can dock your complex with similar binding site parameters in different docking programs and can compare the results.
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To proceed with the docking, I need to find the chain for the protein. Can someone help me with this? How to find the chain?
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For this, you should have the 3D structure of the protein (X-ray or Homology model). The structure can be obtained from PDB or modeled at SWISS-MODEL. If the ligand is bound with a protein chain then you can select that chain for docking purposes. Moreover, if there are multiple structures available you can superimpose a few of them, and from a well-aligned cluster select the appropriate one. During selection, keep a few points in mind, for example, sequence of the protein is from a desirable source, resolution <2Å, lesser gap, or mutations, bound with well-known ligand, etc. If there is no ligand-binding information available, then you can predict the binding site using several web servers, eg. CASTp
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I have designed around 200 ligand molecules for inhibiting a protein. I am a bit confused with the sequence of filtering them, in order to select the best molecules for conducting MD simulation. I have been using autodock 4.2 with 1000 to 2000 runs for blind docking. And I am having problems deciphering and analyzing the results, since clustering takes forever, and the result was not so straight forward to analyze. so I decided to use Vina for blind docking the results were more desirable. so I was wondering if it is a valid method, do other researchers use Vina for blind docking?
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Authodock via is not suited for blind docking and leads to errors. For blind docking there is a modification of Authodock vina named qwickVina https://www.nature.com/articles/s41598-017-15571-7 It's easy to istall and really faster than canonical version, however the docking algorytm remains the same.
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I need to perform a covalent docking between a specific residue in my protein structure and glutaraldehyde as a ligand. I have tried few programs but I don't know how to identify my ligand as they use unspecific libraries and when I import the molecule myself the docking doesn't start running. I would like to know if anyone has any experience regarding this matter.
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Normally you will need to in some way tell the program which are the reactive groups
How to exactly do ligand preparation for covalent docking depends very much on the specific program you use,
If the program you are using offers a tutorial with sample data, I strongly suggest that you first do the tutorial to be better able to discern at which step the procedure with your own ligand goes wrong:
e.g. for Autodock
omparative Evaluation of Covalent Docking Tools
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Dear Researchers
I am using Autodock-Vina for small molecule docking, I have a library of molecules around 400,000 and I have minimized ligands by MMFF94 and converted them into PDBQT file using Openbabel.
when I look into the pdbqt file number of active torsions are different from no of rotatable bonds.
In the following example number of active torsions are 9 and number of rotatable bonds for the same molecule is 11.
REMARK 9 active torsions:
REMARK status: ('A' for Active; 'I' for Inactive)
REMARK 1 A between atoms: C_1 and C_2
REMARK 2 A between atoms: C_2 and CA_3
REMARK 3 A between atoms: CA_3 and C_4
REMARK 4 A between atoms: CA_3 and N_6
REMARK 5 A between atoms: C_7 and C_9
REMARK 6 A between atoms: C_9 and O_10
REMARK 7 A between atoms: O_10 and C_11
REMARK 8 A between atoms: C_27 and C_29
REMARK 9 A between atoms: C_27 and C_30
Is it mandatory to have an equal number of active torsions are and the number of rotatable bonds?
Please let me know the way to specify the number of torsions in the ligand preparation (command line ).
Thank you
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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)"
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I am docking three ligands with more than one proteins. Two of the ligands are already approved drugs and third is a plant compound. My all ligands accepts gasteiger charges and docking went smooth. I have also performed docking by adding kollman charges but my two approved drugs were not getting charges as the pdbqt file was not getting saved by adding gasteiger charges but i was able to get pdbqt file of plant compound successfully and interestingly I have got more negative binding energy values for plant compound by adding kollman charges than gasteiger charges. Is it normal to add kollman charges to ligands? can i report it? And as I have to compare all the ligands. Can I add in my paper the values of plant compund with kollman charges?
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Nishat Malik,
Kollman and Gasteiger charges need to be fitted appropriately based on the nature of the ligand- either it is synthetic or a plant compound. As you had mentioned, your study contain both synthetic as well as plant compound, standard docking can be performed for all the compounds with same charges, further, residues has to be checked properly. This step is for preliminary standardization. Based on the obtained binding energy values, cluster and reference RMSD values (Root Mean Square Difference) and Ki values (Inhibition constant), further alteration of Kollman and Gasteiger charges can be carried out and further docking should be performed. Maximum negative values are an indication of maximum binding affinity of the ligand molecule. If your plant compound possess higher negative value, it indicates that your plant ligand has more ability to inhibit the corresponding target protein molecule.
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Is there any free software available that can provide me with information about the docking of any nanoparticle or a drug on bacterial surface proteins??
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AutoDockTools will be a good software for docking. Identify and prepare the bacterial surface protein of interest and interact with the drugs
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I am using PyRx as platform when I load macromolecule and ligand, the molecules get loaded. When I Dock I get this message "<PyRx.autogridPage.RunAutoGrid; proxy of <Swig Object of type 'wxPanel *' at 0xb7b94c0> >>Python 2.6.5 (r265:79096, Mar 19 2010, 21:48:26)"
Can anyone help me in resolving this issue
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First of all check your macromolecule maybe you miss a step in optimization and energy minimization.
2nd use grid box @ 60,60,60. because the macromolecule is more flexible 60,60 grid.
And make sure you use the correct active site of your known protein.
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I am currently working to dock a ligand at a receptor and working on autodock 1.5.6 and the map files are not being generated , as the autogrid run is unsuccessful, I have previously done this but this time I am unable troubleshoot as to why .gpf file is not being able to generate or being able to be read by autodock?
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Try out this method.
1. open the .gpf file in notepad and type ''Parameter_file AD4_parameters.dat'' as the first line in the notepad.
2. save the file and execute the autogrid
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I trying to install vina using pip and get this error(see file). I think the problem is that boost is not added to path. I have tried various tips posted on stackoverflow threads, read the boost docs for working with python and even watched the videos about how to install boost, but have not been able to solve this problem.
Apart from using pip I tried to install via conda following this manual:
Error not fixed. How i can add boost to path? After installing boost via bootstrap.bat and then .\b2 i get 2 links, but if i add it to PATH variable it doesn't solve this problem. I want to try use Vina scripts in python file
Has anyone been able to install Autodock Vina via pip or conda?
Brief output:
...
ValueError: Boost library location was not found!
Directories searched: conda env, /usr/local/include and /usr/include.
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Artem Petrov You can use the WSL/WSL2 in Windows to simulate a Linux environment, then you can use conda in it.
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Hello everyone
Can I use Vina to dock analogues of nucleotides triphosphates into a polymerase active site coordinating Mg ions?
The ions are also typically in coordination with water molecules to satisfy their proper geometry.
Is it possible to do such docking while, at least, Mg ions are kept at the active site?
If not, is there any open-source docking tool to to such docking?
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Check out the answers to this question: https://www.researchgate.net/post/How_to_Mn_based_metal_atom_parameter_add_to_autodock, they are also valid for other ions that are not recognised by default.
get the parameter file from http://autodock.scripps.edu/resources/parameters/AD4_parameters.dat/view and follow the instructions kindly provided by @Nur Aqilah Zahirah Norazmi
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I want to dock a handful of ligands to a receptor. I found out that the new fork of autodock, autodock-gpu, has been developed for accelerating docking process by using gpu instead of cpu. I was wondering if it is possible to utilize the google colab to do this.
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Yes! You can do that, just include the whole protein inside the grid box for blind docking.
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Good evening everyone, I am experiencing this error when I tried to open my dlg file in AutoDock. Can anyone explain this error? Thanks
Traceback (most recent call last):
File "C:\Program Files (x86)\MGLTools-1.5.6\lib\site-packages\ViewerFramework\VF.py", line 898, in tryto
result = command( *args, **kw )
File "C:\Program Files (x86)\MGLTools-1.5.6\lib\site-packages\AutoDockTools\autoanalyzeCommands.py", line 3852, in doit
d.readDlg(dlgFile)
File "C:\Program Files (x86)\MGLTools-1.5.6\lib\site-packages\AutoDockTools\Docking.py", line 105, in readDlg
self.ch = ConformationHandler(self.ligMol,
AttributeError: Docking instance has no attribute 'ligMol'
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Dear Sheng,
This problem is very easy to solve
You must create your research folder on drive C.
for example
C: \ new
(Do not create in C:\Users\alion\Desktop\new)
Good luck
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Hi,
Our wet-lab results inhibit bacterial growth against certain compounds. We are interested to predict its possible targets from bacteria. I came to know about Inverse docking but I did not find any software or server to use it. There are a couple, but they are somehow not responsive.
If anyone has handled such things, I would be grateful to hear them.
Cheers,
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Check ChEMBL for activity data for your compounds or compounds similar to yours.
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I am a beginner in molecular docking. And I want to know is the active pocket of the receptor the same for all ligands? Or will there be different active pockets for different ligand receptors? I want to do a hydrolase docking with a small carbohydrate molecule, I want to know exactly (or roughly) which part of the active pocket is in (I hope that the binding energy will be lower after docking), so how do I determine which range the active pocket of the receptor is in before docking? Looking forward to your response!
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This's an interesting question. There are several ways to find the binding site of proteins.
1- As the respected colleagues answered, using online databases, you can do it.
2- For all crystallographic structures available in the PDB database, the binding site of target proteins can be accessed through the paper that published the relevant protein. In this case, you can search for your protein in PDB to find its binding site.
3- Using blind docking. Blind docking is a procedure in which you can dock several ligands with different backbones into target receptors to evaluable the possible interaction between these ligands and protein surfaces in different areas. Based on docking energies, you can categorize your ligands and find relevant sites that are the most important locations for interactions of your ligands. This method, in some cases, works fine, and it is a reliable way to find the binding site of proteins.
4- Using the PDBbind database. PDBbind database consists of many experimentally assayed binding modes of ligands and receptors. You can download it and check its content for relevant data.
5- Using text-mining approaches. This method will enable you to use artificial neural networks to excavate the literature to find the binding mode of ligands into your target receptors. In this way, you can find many papers dealing with your project and use their content to predict the binding site of your protein.
6- Using PSI-BLAST. This method is a time-consuming procedure but returns validated results. For this case, you can blast the sequence of your query against the PDB database and find more similar proteins. Based on the location of other protein active sites that showed similarity with your protein sequence, you can find some binding sites in your protein structure. Please note that the alignment output can be submitted to ENDsprit software to compare the results and align the studied sequences' binding site.
Helpful papers:
These papers can help you to know more about the prediction of protein active sites:
Good Luck
Rasouli. H
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I have taken B cell epitopes from consensus protein and overlapping T cell epitopes from B Cell epitopes having MHC class I and II binders. Is is enough if I just dock B cell epitopes with protein or do I need to separately select and dock T cell epitopes too.
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Hi Ramin Ekhteiari Salmas,
Computational appraoches (reverse vaccinology) incorporates our understanding on the immuno dominant epitopes derived from various studies over the decades.. MLM, ANN, SVM are some of the networks often used in identification of putative vaccine candidates. It aids to predict or identify the candidates without consuming our time, cost of the assay and requirement of highly specialized laboratories . Further, an epitope predicted by the software is not considered as final product and directly pumped into the vaccine production pipelines. After prediction, it also goes several round of experimental assay for the production of antibodies, evaluation on production of auto-immune antibodies, toxicity, etc. followed by various clinical phases or trails as recommended elsewhere.
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If a receptor is new, no data in PDB, literature regarding its active site, Should I perform blind docking??
If a receptor is new , model is in PDB, ligand bounded, then should I perform docking it those active sites where ligands were bounded (in PDB structure) or should I perform blind docking ??
or in any case should I perform site specific docking using CASTp or other active site/pocket predictor
Please help, Thanks.
Sincerely--
Sunzid.
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Hi
Blind docking is the first stage of checking the docking interaction of a compound with a protein. When the protein is new, generally we have to do the blind docking and binding site prediction etc.
It you got a protein-ligand complex or a protein which is bound with the ligand, then choosing this protein PDB will be better.
You may check this
All the best.
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Is it necessary to repair the missing residues on AutoDock Vina if they aren’t my selected residues? Would it affect my docking results?
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Dear Yie Woon Chong, I agree with Sutanu's answer. Docking in Vina is usually done in a semi-flexible way, i.e., the receptor is rigid and the ligand is flexible. In this scenario, residues far from the binding pocket won't affect the results. The same even in the case of "flexible" docking in Vina - it still keeps the protein rigid, and only a few selected residues are allowed to move, so, again, distant missing residues won't disturb the results.
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