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Molecular Docking - Science method

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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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In mgl tools autodock 8 no of torsion possible. During ligand prepration you choose torsion as per your objective. It's possible to change torsion in ligand
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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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You can compute the interaction energies (vdW + electrostatic) that will tell you which interaction is contributing to favorable docking.
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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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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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Dear all,
I tried docking my protein heterodimer to form a hexamer (trimer of a heterodimer) using symmdock server. The output results has given top 20 models of the hexamer and I opened the top model into PyMOL. I see the the parental template has intact structure while the generated partner structures are all broken in the PyMol (Picture attached). When I opened it in coot all the atoms are present and display very well as atoms. But somehow it is messed up with the cartoon representation in PyMol. Please suggest, how can I fix this issue.
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You need to make sure from the beginning (before docking) that the "receptor" and the "ligand" do not have the same chain label! You can change chain labels using the "alter" command in PyMol ( https://pymolwiki.org/index.php?title=Alter&redirect=no )
alter (ligand and chain A), chain='B'
changes the chain label in object Ligand from A to B
You can force a proper display of your faulty complex by using the "retain_order" setting in PyMOL ( https://pymolwiki.org/index.php/Retain_order )
set retain_order, 1
but the ambiguous chain labels may cause problems with a number of other commands and further evaluation of the complex in other programs!
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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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We are looking for receptors in order to perform in silico studies of some antalgic and anti-inflammatory ligands isolated from plants and have been tested in vivo.
A part from COX 2, IL-6, TNF-alfa, could anyone propose other important receptors?
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You can go for NF-KB, IgA IL-1, Toll-like receptors, RIG-I-like receptors, NOD-like receptors, and C-type lectin receptors.
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I am beginner in molecular docking field. I have read a lot research papers and books but I wanted a suggestion about any material that could help me clarify ideas about the biophysical basis of molecular docking.
Many thanks.
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When I run autogrid4 it says: autogrid4: ERROR: Unknown receptor type: "Se" -- Add parameters for it to the parameter library first!
How do i handle it? Thanks
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Hi,
At first, you should add the Se atom parameters to the AD4_parameter.dat file.
Se parameters:
atom_par Se 4.21 0.291 14.000 -0.00110 0.0 0.0 0 -1 -1 4 # Non H-bonding
Save and paste the modified dat-file to the folder whit the autodock4 and autogrid4 exe-files (C:\Program Files (x86)\The Scripps Research Institute\Autodock\4.2.6).
Thereafter, you have to add the following command "parameter_file AD4_parameters.dat" (without quotes) to the top of the gpf- and dpf-files.
Now the AutoDock is ready for docking of the Se-containing compounds :)
A similar question was also resolved here:
Good luck!
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I have prepared a drug library (energy minimized & conversion to PDBQT) in PyRx but while performing molecular docking in PyRx I am getting some false results. Can I run molecular docking in separate AutoDock Vina with PyRx prepared ligands?
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Yes, agreed with all
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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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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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Is there a way to generate a list of SMILES (Simplified Molecular Input Line Entry System) from a list of compound names (in Excel)?
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you may use this online tool for generating SMILES
First you have to save your structure in mol format then you can upload here or directly draw.
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Can the differently coloured region around the ligand be saved so that I can directly see the coloured region the next time I open it? If so, what format would be the file? pdb format? Thank you.
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To preserve all the information of a ChimeraX session, you have to save it as a session file (extension .cxs). This enables you to continue the session from exactly the point where you saved it, colouring, orientation and all.
Saving as .pdb would only save the coordinates, no ChimeraX specific information.
You use the .pdb format (or .cif) to transfer the coordinates to other programs which cannot interpret the chimeraX specific information.
See https://www.cgl.ucsf.edu/chimerax/docs/user/commands/save.html to see a listing of all supported formats, and which part of the session they cover - the session file is the only one that covers all the information in your ChimeraX session - but it can only be opened by ChimeraX! All other formats only export the part of the information that can be interpreted by a particular class of other programs, e.g. images, that are 2D views that you can print or insert into a word processing file or a powerpoint presentation.
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I need this file as I have to study the interaction with a protein target through the FLAP (molecular discovery) software and I would like to understand where to find this file or how to draw it on ChemDraw, maybe in SMILE format. Thank you
Latex Beads, Amino-modified polystyrene
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Dear Gianfranco, it is highly doubtful that you can find polystyrene nanoparticles in a ready-for-docking form anywhere. You have to model it from scratch using Materials Studio or any other suitable modeling software.
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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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Colleagues, I need suggestions for PDB complexes with ligands (organic molecules) that prove difficult to validate by redocking, regardless of the program. Suggestions in the comments, and thanks in advance for your help.
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Sir,
I would like to suggest a HSP90 protein with PDB ID: 1YET.
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Hello, I'm working on interactions of some inorganic metals/compounds with some protein of interest. Here the ligand are in nanoparticle form. So as for ligand preparation for docking these need to be in nanoscale range, is there any procedure for preparing it ?
Please suggest some user friendly software other than Vesta if possible!
Thanks in advance.
Regards,
Vinay
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Mohammad Kooti Sir, Thanks for your interest. Actually here the metal compounds that are needed to be converted to nanoparticles will be later subjected to molecular docking analysis with the protein of interest that's why I'm referring to them as ligands. Please guide how to use vesta for such conversion.
Regards,
Vinay.
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I have some apoptotic proteins identified from breast cancer datasets. I have a general queres in my mind.
1) How does apoptotic proteins function in cancer cells?
2) Would inhibiting an upregulated apoptotic protein would be feasible via molecular docking if we are aiming for a therapeutic alternative?
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Dear Dr Sing,
To find the function of proteins you can use uniprot database or genecard.
Before molecular docking, you should check the druggability of your protein by pockdrug. By molecular docking and MD you can find best compounds
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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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Can someone recommend a comprehensive and up to date textbook on molecular docking?
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1. Molecular Docking for Computer-Aided Drug Design
Fundamentals, Techniques, Resources and Applications
2. Molecular Docking and Molecular Dynamics
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I am doing molecular docking with a flavoprotein, but the results show that the cofactor is not being taken into account, since the spaces are overlapping as shown in the image. I am using Autodock VINA. How can I make the software consider the FAD? Or, what other software do you recommend to make this docking? I am interested in the interaction with the FAD because the inhibition forms a covalent bond with the cofactor, although I do not see the formation of bonds, I am interested in it being in the interaction calculations
Thank you very much for your help.
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Your best chance of getting an expert answer is by posting this question to the autodock mailing list - this is where the real experts are
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I tried many alternatives but unfortunately, I could not find the best and equivalent alternative which works properly on mac system!!!! May anyone working in the field of molecular docking guide me with the free suitable software??
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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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After performing Molecular Docking between Protein-ligand complex in Autodock vina, how do we validate the results to be accepted? Is Molecular Dynamic Simulation help in doing so? Please provide a detailed explanation for the same!
Thanks in advance.
Regards,
Vinay
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I have done MD simulation and want to interpret and plot the data from the files. As my PC did not have enough specs for Dual boot OS because the XmGrace tool is supported only on Linux. Though, I have found an alternate known as QtGrace (https://sourceforge.net/projects/qtgrace/) for plotting the data. How far is the software is reliable as XmGrace?
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Thank you Aashish Bhatt !
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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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Hi. I want to convert ~4000 ligands in .sdf files into .pdb or .pdbqt format for molecular docking. I used " >obabel *.sdf -opdb -m " command but the structure of the ligands changed drastically. attached is one of the ligand after conversion.
Is there any way of converting all ligands simultaneously without compromising its structure?
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Dear Tengku Kamilah
Try to download your sdf structures in 3D formats not 2D
Then, Run this code;
Firstly, splitting into separate files ;
$ obabel -isdf 4000.sdf -osdf -O *.sdf --split
Then, Energy Minimize:
obminimize
obminimize -ff MMFF94 -n 1000 *.sdf
Third to pdbqt:
$ obabel -isdf *.sdf -opdbqt -O*.pdbqt
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Recently am learning molecular docking so I need list of phytoconstituents which having any Medicinal value and also am going to study the docking of protein and phytoconstituents
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here you can type the name of the plant of your interest and it will display the list of related phytoconstituents for the same.
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I am using Molegro Virtual Docker for molecular docking wherein the user can render flexibility of the chains of the receptor by softening the potential. This is usually done by increasing the side-chain flexibility tolerance. I would like to know what advantage does this feature provide and how does it affect the authenticity of the result?
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Docking, whatever the algorithm and platform, only makes sense for proteins with known structures (x-rays, NMR, etc.) with their bound water molecules. If you use modeled proteins, you must first subject them to a few cycles of molecular dynamics in water. If so, you can accept the results considering what Martin said.
Greetings
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Also, how can we perform an energy minimizing steps for ligands ?
Thanks in advance !
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Hi, you can convert 2D or 1D (SMILES) molecule file into 3D molecular structures using different ways, such as:
1. Using OpenBabel as a standalone tool, https://sourceforge.net/projects/openbabel/
2. OpenBabel as web-server, http://www.cheminfo.org/Chemistry/Cheminformatics/FormatConverter/index.html (Comparatively easier approach)
3. Using ChemDraw/ MarvinSketch etc.
For energy minimization, you may use
2. If you perform docking using PyRx/ Glide or some other sophisticated software, they have options for energy minimization before docking.
Watch some YouTube tutorials to get more insights about the tools.
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I have docked complexes generated by flexible docking via AutoDock Vina. To some extent, flexible docking introduces poor rotamers in the residues specified by user to be flexible. Is it possible to optimize the docked complexes prior molecular dynamics simulation? If yes, kindly mention the tools to do so.
Thanks
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It depends which software you'll use to perform the MS simulations. Most of the tutorials of GROMACS show how to perform the energy minimisation (that can correct these bonds). Usually, the steps for a MD are: minimisation, equilibration, and production (the MD).
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Hello, I am using CDOCKER of BIOVIA Discovery studios for Molecular Docking. I need to compare the binding affinity of small molecules to my protein target. I am doing a comparative analysis. My small molecule has a CDOCKER score of -3. I am trying to find better binding molecules than this molecule. I have my CDOCKER scores of positive (For ex.65, 79, etc) and negative values (For ex. -11,-35, etc). I need help in analyzing the binding based on scores. I have read that the high score value determines high binding affinity. Should I consider high positive value or high negative value as high binding affinity? what does the negative sign indicate? Need help on this.
Thank you in advance
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Thank you all for the replies. I will do the same.
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How can I add atomic parameters for the ions Europium (Eu3+) and Americium (Am3+)
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How can I get Autodoktools to recognize boron atoms?
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Dear Researchers and Professors, recently I faced some doubt in molecular docking energy result. Herewith I have enclosed CDOCKER (Discovery studio software) energy values of some docked molecule. Generally in literature mentioned, negative docking energy values indicates more binding energy. In following attached image which molecule has more higher binding interactions? Kindly explain. My doubt is in the result table commonly mentioned (-CDOCKER energy). Means the all the positive values are considered as a negative value or not?. Some time the values shows in negative values.
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Energy scores in the docking process are various. you should read the detailed manual of cdocker. for the score, generally positive and highest prices are chosen for the best poses for docking results.
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Hi everyone, im working on molecular docking and im interested on introducing a phosphorylation on a specific residue of a 3D protein molecule on PDB format, so that i colud evaluate conformational changes. My question is, is that possible? and if it is, which bioinformatic tool could you recommend me for it?
Thanks
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You can also use the CHARMM GUI web site for this purpose, regards
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While working on molecular docking, in the process of the protein preparation when i added the polar hydrogen the system throws an error given below. An explanation of the error and a solution to work it out would be highly appreciated?
Thanks in advance!
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There are errors in the file you have used, i.e., the protein file.
First open the file in notepad and remove the unnecessary atoms, including water or any other solvents.
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I want to conduct molecular docking and dynamics of silver nanoparticle (AgNP) with protein. Is it possible to make a silver nanoparticle model using ChemDraw? Do you have any suggestions to do that? Thank you.
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Yes, the Chemdraw app can do it; simply draw a two-dimensional structure first, then convert it to a three-dimensional structure if desired.
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Hi
I would like to do molecular docking for my protein with metalloids such as arsenate, nitrate, selenate. I am able to dock for nitrate and selenate on the CB dock website. However, I am getting errors when I try to do that for arsenate. Is there a way to find why the error message and how to fix it in CB dock? or please suggest good and reliable free software for docking in Mac OS? I have the latest version of OS software (Monterey).
Please suggest or recommend, how to perform this work.
Thanks in advance
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Sure thanks Naeem Abdul Ghafoor . I will try these things
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This has been our problem since it is our first time to undergo molecular docking. We are looking the Nav1.5 channel’s sequence from punlished articles yet we still want to know the exact method on how to determine these.
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The first thing to do is to learn what is experimentally known. Usually, I would search UniProt directly with the sequence. Since I could not find Nav1.5 directly in UniProt, my go-to place for protein sequences and associated information, I did a general Google search to find alternative names.
From GeneCards I learned that the gene name is SCN5A. With this name I searched UniProt: https://www.uniprot.org/uniprot/Q14524 is the record for the human homolog, https://www.uniprot.org/uniprot/Q14524 which not only gave me the sequence and location of the transmembrane segments, but showed me that an EM structure is available in the PDB: ( https://www.rcsb.org/structure/7DTC )
You can look at this structure using a molecule viewer, e.g. PyMOL. If you color the structure by secondary structure, the loop/turn segments will stand out (green in the attached image) and are indicated in the same color in the sequence line.
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So far, when I looked on molecular docking papers, it often involves using a protein as the receptor molecule, with ligands like another protein, nucleic acids, or small molecules. I have also found the application of RNA or DNA as the receptor molecules, docked against another RNA or DNA, and small molecules. However, I never (yet) found a paper referring of using other polymers as receptor molecules, like lipid or nanocarrier polymers (like chitosan or cellulose or even carbon nanotube). Is there a reason that nobody does that? Or some research groups have already done that? I am just curious.
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These things are already mentioned in many papers. We recently did the same analysis against SARS CoV-2
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I want to perform targeted molecular docking of:
(a) a receptor (enzyme) whose structure is not availabe, and hence has been built by computational ab intio methods (and not homology, since the % identity is very low);
(b) a substrate whose structure is availabe.
Given that, the active sites of the enzyme are also not truly available, but has been obtained from (a) literature review; or
(b) inferred from cavities/clefts predicted by CASTp results, how exactly should I perform targeted molecular docking?
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Hi. I am currently designing peptide ligands.
I noticed that DUD-E (Directory of Useful Decoys, Enhanced) can be used to generate decoys for small molecules. I wonder if DUD-E is equally useful in generating decoys for the peptide ligand.
Is there other way of decoy generation for peptides?
Thank you.
Sincerely yours,
Thai Leong
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A good decoy would be randomizing the sequence of your query peptide, an construct some of them. This would give you a set of same length peptides with the same aa composition. This is similar to the procedure in BLAST for estimating E-values for alignments
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Hi Guys, 
I am trying to apply a phosphorylation patch (THP2) to THR residue in VMD, but every time I am having a weird kind of phosphate conformation (please see the attached image).   Is there any problem in my .pgn file, 
topology top_all27_prot_na.rtf
topology toppar_prot_na_all.str
pdbalias residue HIS HSE
pdbalias atom ILE CD1 CD
pdbalias atom GLY OXT OT1
segment P1 { pdb ash.pdb
}
patch THP2 P1:285
regenerate angles dihedrals
coordpdb ash.pdb P1
guesscoord
writepdb AB.pdb
writepsf AB.psf
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Ashfaq Ahmad The problem can be solved following these correction in :
- Topology file
The main problem is, while you are creating your phosphorylated residue, vmd tries to create an "OT" oxygen at the end of the molecule, following the topology as a normal SER. Meanwhile, a normal SER its been created, a pSER has simultaneously been created (with oxygens named O1P, O2P, and O3P). So the connection between oxygen at phosphate organization corresponds only to the creation of an OT between O2P and O3P. Reading the pdb file after its creation by vmd scripting you must find something like these:
ATOM 7518 N SEP P 553 -38.537 8.718 -0.212 1.00 0.00 P N
ATOM 7519 HN SEP P 553 -39.467 9.069 -0.287 1.00 0.00 P H
ATOM 7520 CA SEP P 553 -38.248 7.843 0.882 1.00 0.00 P C
ATOM 7521 HA SEP P 553 -37.231 7.893 1.241 1.00 0.00 P H
ATOM 7522 CB SEP P 553 -39.092 8.219 2.155 1.00 0.00 P C
ATOM 7523 HB1 SEP P 553 -38.857 9.302 2.234 1.00 0.00 P H
ATOM 7524 HB2 SEP P 553 -40.167 8.031 1.949 1.00 0.00 P H
ATOM 7525 OG SEP P 553 -38.722 7.488 3.280 1.00 0.00 P O
ATOM 7526 P SEP P 553 -37.749 8.007 4.367 1.00 0.00 P P
ATOM 7527 O1P SEP P 553 -36.917 9.154 3.897 1.00 0.00 P O
ATOM 7528 O2P SEP P 553 -37.181 6.847 5.030 1.00 0.00 P O
ATOM 7529 OT SEP P 553 0.000 0.000 0.000 -1.00 0.00 P O
ATOM 7530 O3P SEP P 553 -38.612 8.580 5.463 1.00 0.00 P O
ATOM 7531 H3T SEP P 553 -39.191 9.322 5.270 1.00 0.00 P H
ATOM 7532 C SEP P 553 -38.565 6.413 0.498 1.00 0.00 P C
ATOM 7533 O SEP P 553 -39.765 6.137 0.343 1.00 0.00 P O
In bold appears the false OT atom created, forming eventually the triade as a weird phosphate organization. The problem cant be solved by editing this file, erasing the false OT atom, and renumbering the following atoms to be according to the previous ones.
The only solution I found was correcting the TOPOLOGY file, specifically, the phosphoserine topology changing the name of OT atom at patch part in topology file from OT = O3P, O3P its the normal OT name at phosphoserine, but the bivalence between OT and O3P its the main error that's become in a weird conformation.
Must be seen in the topology file like these :
##################################
# PREVIOUS TOPOLOGY PHOSPHOSERINE #
##################################
ATOM CB CT2 -0.08 !
ATOM HB1 HA2 0.09 !
ATOM HB2 HA2 0.09 !
ATOM OG ON2 -0.62 !maintain NA atom type
ATOM P P 1.50
ATOM O1P ON3 -0.82
ATOM O2P ON3 -0.82
ATOM OT ON4 -0.68
ATOM HT HN4 0.34
###############################
# AFTER TOPOLOGY PHOSPHOSERINE #
###############################
ATOM CB CT2 -0.08 !
ATOM HB1 HA2 0.09 !
ATOM HB2 HA2 0.09 !
ATOM OG ON2 -0.62 !maintain NA atom type
ATOM P P 1.50
ATOM O1P ON3 -0.82
ATOM O2P ON3 -0.82
ATOM O3P ON4 -0.68
ATOM HT HN4 0.34
In this manner, the creationg of PDB and PSF files, follow the idea of creation a phosphoserine without OT oxygen, with a normal phosphate coordination.
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Nattokinase, as far as i know, dont have a particular catalytic sequence (correctly if i'm wrong, i havent found any article that state it has it). I would like to ask if anyone know a procedure to determine, bioinformatically, the site of digestion of a protein by Nattokinase
Thanks in advance
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As a serine protease, the structure is well known for a wide range of proteins and organisms and you could try to find similar proteins via BLAST using the RCSB database.
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Sometime this may be a silly question because I'm new to this field.
In 3Drefine server, it mentioned that it applies atomic-level energy minimization on the optimized model using a composite physics and knowledge-based force fields. My question is,is that refinement and energy minimization both do the same change to a structure or they are different. If these servers do different changes in structure, shall i need to go through both servers before do my protein-protein molecular docking
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Waseem Ahmad Ansari Thank you sir. I try
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I have this protein (regulatory protein) from PDB that has missing residues not on the active site but on the site where the protein can bind to other protein. So, I use it in molecular docking since it located far from the active site.
However, when I want to do the dynamics, I'm thinking about using the same proteins but have fixed missing residues by using AlphaFold2 generated protein.
Is it valid? Or I should just using modelling-based proteins in docking too?
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Thank you Marwa Abd El Kader Zaater, Nayim Sepay, and Vinnarasi Saravanan for the answers!
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I need someone who understand results from Triple TOF LC/MS/MS of medicinal plant extract, who will assist in interpreting and my results and may wish to be a co-author with me when publishing my findings (which include molecular dockings)
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I can help you in this field
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Hi!
The following error showed up while i was converting some small molecules from sdf to pdbqt in OpenBabel from PyRx:
<<bound method VSModel.PrepareLigandMol of <PyRx.vsModel.VSModel instance at 0x091D8EE0>>
Any tips?
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Convert your .sdf file directly using openbabel to mol2 and then .pdbqt. Hope it would work, sometime openbabel gives this error when you are asking for the same (not supported format).
Secondly, if this also don't work kindly convert your .sdf to .pdb and convert it to .pdbqt using autodock.
Good luck Julia Gomes
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if we add molecular docking score to a review paper, can we publish the paper to good impact factor journal?
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This is totally up to you. If you want to add it you can, researchers mostly add it at the end of a research proposal that this much work has been done so for and these are my further suggestions. For validation of these insilico outcomes in the wet lab they ask for funds.
Good luck Farhanul Islam
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I want to perform molecular docking between a receptor and a ligand molecule, but the ligand molecule is a linear chain (eg: nonacosane). I have downloaded the structure from PubChem. Is it okay to proceed with the docking analysis? Or do we avoid using linear structures as ligands during the docking process, as they tend to bind to any surface?
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Linear molecules have more conformational flexibility, therefore you will probably work with an ensemble of conformations available to the ligand for docking, or go for flexible docking, as you would for a peptide. As complex formation decreases the conformational entropy, the flexibility reduces the binding energy. Even when starting from a flexible lead compound, constraining the overall flexibility of the ligand to the actual binding conformation can improve affinity, therefore these leads are developed into more rigid cyclical compound in drug development.
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Hello everyone
I have numerous molecules with such complex configuration. The structure normalizer node of RDKit in KNIME can't handle these compounds and throw them as "failed". OpenBabel also can't do the job.
How can I prepare them (3D generation and energy minimization)?
Thanks
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You can convert this structure to SMILE and show the 3D in Chimera, and minimize energy. You can save this structure to pdb or mol2.
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Hello!
I have a few questions related to molecular docking and its analysis. I used Ligplot+ to analyse my docking results.
  1. When a mutation occurs for a Ser residue (S188F, Mediterranean variant of G6PD), I noticed that the active site residue (His263) shifts from hydrogen bond interaction to hydrophobic interaction. Is there a reason for this?
  2. Apart from that, while performing molecular docking, is it important to include all important residues inside the grid box? (when I did that, the ligand did not bind to its active site but when I made my grid box smaller and included the active site residue, it bound to the active site.)
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the effect at the structural level can be seen in the non-covalent interactions. The hydrogen bonds can be analyzed since the amino acid serine that has a hydroxyl group is lost with the mutation to phenylalanine. Furthermore, there is also an effect on the polarity of the active site and it can be calculated with the hydropathic index.
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I was tried to dock Cucurbit[7]uril with protein in Autodock vina, but the ligand structure i.e., the structure of Cucurbit[7]uril was planar (taken from the pubchem or other website everywhere the same planar structure was available), whether in all the research papers the pumpkin like 3D structure having a cavity to interact with the guest molecule were reported. I am very new in this field, so, I could not convert it to the 3D structure. Can anyone help me to solve this problem? It will be very helpful to me.
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Annemarie Honegger thank you madam
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I can do docking with autodock vina. But it shows me several answer of same thing in several time. So, i am looking for some other free software or link by which i can make docking. Thanks in advanced.
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I have tried PDBePISA to calculate the free binding energy for the protein-DNA docked complex structure. However, I am still looking for the other programs (online available) that can give a comparison of the binding energy. Please suggest some reliable online server that can give those values.
Thank you in advance
Best regards
Prem
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Free energy is a property if an ensemble. Single structures cannot yield consistently accurate predictions.
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Molecular docking energy of molecules like quercetin & apigenin etc. are documented wrt PDB ID 5 IKR as inflammatory marker. But is we use the combined in a drug, how can the synergistic effect be tested? or will the lowest energy molecule fit in the active site first & the rest in stage 2 if space remains?
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If both the compounds allowed to interact with the protein simultaneously, follow can happen.
One molecule can bind to an active site of a protein at a time. Therefore, the high -ve value compound between your molecule under investigation will bind first at the active site. After that the second compound can bind to a site other than active site.
In this case, you have to dock both the compounds with the protein individualy to find the high -ve value compound. After it, the structure will be considered as input file for second docking..
It may help you... Best of luck.....
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I faced a FATAL error while preparing Docked Proteins for MD simulation using Amber20.
But this error does not occur while performing with non-docked protein structures. Is this problem is due to Autodock?
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Hi Jagadeesha,
The following tutorial can help you:
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Molecular docking, one ligand two or more targets simultaneously, is it possible? Any suggestion?
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Usually simultaneous docking with more than one protein is uncommon. This article may help.
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I want to find a proper inhibitor for an enzyme. The traditional inhibitor has been proved to construct a covalent link with the active residue of the enzyme. Is it possible to predict if my compound can construct a covalent link with the residue (using computational methods such as molecular docking)?
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Talia Serseg Nayim Sepay Thank you very much for your help.
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Hello everyone
I wanted to dock NQO1 and p53 (protein-protein docking).
NQO1 (a homodimer) is a quinone reductases which has FAD bound to both of its active sites. In order to catalyse the reduction of quinones (its substrate), the FAD within the active site has to be reduced to FADH2 by the oxidation of NADPH which then makes way for the incoming quinone (ping-pong mechanism).
NQO1 is also known to protect p53 from Ubiquitin independent 20S proteasomal degradations and so mutations affecting NQO1 could alter p53 stability (this is my study interest). In pursuit of investigating this association, I want to dock p53 with NQO1 homodimer (having both FAD and NADPH within the active sites).
Now here's the problem
In the absence of a crystallographic structure bearing both the ligands together (FAD and NADPH), I want to dock NADPH first to the NQO1 protein (protein-ligand docking). Being new to docking and after reading multiple threads, I realized that validating my docking protocol is essential.
To validate my docking protocol (done using AutoDock Vina), I considered a crystallographic complex protein (1kbq, https://www.rcsb.org/structure/1KBQ) with two ligands in it – namely FAD and 5-methoxy-1,2-dimethyl-3-(4-nitrophenoxymethyl)indole-4,7-dione and performed the docking of the same complex (I removed 5-methoxy-1,2-dimethyl-3-(4-nitrophenoxymethyl)indole-4,7-dione from the structure and used it as a ligand). Ligand and protein preparation was carried out using AutoDock Tools.
Please note – I tried docking using ligand obtained from two sources
1. Ligand from PubChem (didn’t yield appropriate pose even after energy minimization or reduction of active torsions, Structure labelled B in the figure attached)
2. Ligand derived from 1kbq itself (yielded appropriate pose after reduction of active torsions without energy minimization) (structure A and its derivatives)
As I have learned, to validate my docking, I need to compare RMSD between the crystallographic structure and my docked pose which should be below 2A (pardon me if I am wrong). Although my docking seems perfect (as evident from the last figure, after reducing 4 out of 5 active torsions for the ligand) I have failed to calculate the RMSD. I have tried online servers like COMPARE (https://webs.iiitd.edu.in/raghava/ pldbench/compare.php) and LS-align (https://zhanglab.ccmb.med.umich.edu/LS-align/) but no results. I have also tried comparing the RMSD using Discovery studio visualizer wherein I have used the original crystallographic structure bearing both the ligands as reference by selecting my target ligand in the structure (Structure>RMSD> Set reference) and compared it to my docked pose (out_ligand_1.pdbqt Structure>RMSD>All atoms/ Heavy atoms). The message prompted is
“The following molecule(s) failed due to the number of atoms not matching the reference ligand”
1. Please help me calculate the RMSD between the two structures.
2. Further, by the looks of it (as the docked pose superimposes the crystallographic structure) can I assume that my docking protocol is validated?
If yes,
3. Should I dock NADPH to both the active site one at a time (as there are two active sites within the homodimer) or both the active sites can be docked simultaneously (if yes, kindly guide me)?
4. If my docked NADPH exhibits interactions similar to other ligands (interactions mapped from reported NQO1 crystallographic structures), can I use this structure for protein-protein docking using online servers?
Thanking you for your patient reading.
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try this equation. I have struggled for my project for validation. It helped me
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Hello everyone,
I am trying to do molecular docking using AutoDock Software. One of the struggling I am trying to deal with is generating Grid Box. How can I generate Grid Box without knowing active binding sites of the protein? Should I keep the Grid Box positions as default, or should I change it according to the binding site? Sorry for the inconvenience.
Thanks in advance,
Mervenur
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Dear Mervenur,
I suggest taking a look at the answers to these questions as they may help you to determine if you've taken all the necessary and correct steps:
Best of luck!
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I have already used AutoDock 4.2 and AutoDock Vina and i am trying to validate my docking result form other docking tools.
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Based on energy transfert process, Molecular docking is considered one of the most reliable method to predict the binding mode and binding energy of a protein–ligand complexes which represent an important gain of time especially when we need quick response on a particular process.
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Not my area of actuation, but my gut feeling says it is.
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For example docking of rutin against a certain receptor
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For Docking studies, positive control means any known ligand having reported ligand pose and activity. If your software is able to produce that reported pose, than you can use that particular binding affinity value as a control value.
For rutin, if you have crystal structure of rutin against a certain receptor, try to reproduce that pose using docking method. It will work as postive control.
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Hi
In Molecular dynamics simulation, To test for enzyme stability, We should the enzyme be simulated with and without the substrate.
this means that first we must doing Molecular Docking with substrate, secound doing M.D.
right ?
thanks alot
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You did two experiment in M. D enzyme without ligand and enzyme with ligand
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My ligand has a quaternized pyridine ring in it's structure, but after editing, when I export it from AutoDock Tools as a .pdbqt file and open it in Discovery Studio Visualizer, the structure of my ligand changes and nitrogen appears to no longer be quaternized (a C=N double bond is lost, the +1 charge on the nitrogen is lost, there are now only 2 double bonds in the ring). The rest of the ligand stays as is, the problem appears to be happening only to the quaternized nitrogen. Is there a way to fix this from happening?
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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.
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I am studying drug-protein interactions via Autodock Vina. I got my docking results but the problem is that the drug-target (enzyme) that I am studying has no 3D structure in PDB database. So I build one using SWISSMODEL with a template having 45% sequence identity (no other options). I had to add HEME group to my model via superimpostion using template PDB. I am worried about the accuracy of my protocols and results. Any suggestions on how to minimize errors in such cases??
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Hi
In the absence of a co-crystal structure, the best way to validate docking is drawn through the correlation value of docking scores and bioactivities. Here, you must have a large ligand data set (n ≥ 36).
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Dear experts,
I want to construct the 3D structure of a protein, and I have to insert the related salt bridges to this protein using the itasser server, but I do not know how to do that.
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Hi Alireza anytime and if you tell me your template identity value I am happy to assist you with directing you towards the subsequent step (the chosen template(s) is pivotal in this case especially with a low sequence identity value). :)
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Hi researcher,
I'm really looking for your guidance and help in order for me to pursue my next step in computational work. I'm new to computational work and keen to learn more. Currently, I'm using AMBER 16 to do Molecular Dynamic (MD) simulation and trajectory analysis. The protein I'm working with is 5IBE.  I used CPPTRAJ to extract RMSD'd PDB's from trajectories. I extract specific frames of the trajectory in a 2drms plot, to generate the average structure in PDB format. This is the script I used to generate the average PDB structure from a 2drms plot.
trajin 5IBE_heme_md_pc.binpos 2100 2500
rms first mass @C,CA,N
average 5IBE_heme_md_pc_2100-2500.pdb pdb
2100-2500 is the frame value from the 2drms plot. I have attached my 2drms plot for your reference.
My question is do I need to minimize the average PDB structure that I got from CPPTRAJ analysis before continuing with molecular docking? Is that ok If I continue using this average PDB structure for the docking process without minimization? Please let me know, I need some clarification.
I would be grateful for every suggestion that will be given to me.
Thanks & Regards
PRIYA MURUGAN
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Gabor Balogh
thank you very much!!
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I have searched on PDB but I didn't succeed in retrieve ACE 2 from PDB. Does there any option to obtain this Enzyme.?
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Hi,
is it this one?
RCSB PDB - 1R42: Native Human Angiotensin Converting Enzyme-Related Carboxypeptidase (ACE2)
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I performed a molecular docking on inhibitor namely for example compound A, B and C. Results from the binding energies and Ki from docking show that the potency increased in the order of B>A>C.
However, when conducting kinetic study to measure inhibition constant. I obtained unmatching pattern, in this case the potency of the compounds in the order of B>C>A?
What are the possible factors to influence the results?
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Docking scores rarely correlate with experimental pIC50. It is easier to reproduce binding mode than to predict binding free energy; the latter requires, besides sampling of the conformational space, a rigorous treatment of solvent effects and long-range electrostatic interactions -- and this is computationally expensive. And the purpose of docking is obviously to obtain answers quickly, hence the trade-off.
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I have extracted a ligand from PDB native protein and then used that to dock with my hypothetical protein. The hypothetical protein is phosphopantatheinyl transferase and in PDB the crystalized protein was the same but from another organism.
Now if I perform docking to my hypothetical protein with native ligand (from PDB) and check the complex in PROCHECK Ramachandran plot, will it validate my docking study?? I performed blind docking in AutoDock Vina.
I redocked pdb protein with its native ligand and docked my hypothetical protein with the ligand that I obtained from the PDB protein, but in 2D plot the residues are completely different ? How to validate it?
Please help. Thanks---sunzid
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