Ligand - Science topic

I have all the files: ligand in pdbqt and receptor in pdbqt too.

I keep getting this error when I try to run docking.

I'd really appreciate it if you could help me out.

What are the main in silico approaches to assess the selectivity of a drug or ligand towards a specific receptor subtype, and which computational tools or software are most effective for this analysis?

Thank you for your answers and your participation.

I'm trying to perform a docking experiment using the GOLD software. To do so, I initially prepared my ligand in CHIMERA, added hydrogens and charges (protonation state +3). However, after running my first docking round in GOLD, some hydrogens were not recognized and were labeled as ****. What could be causing this issue? What might have gone wrong?

Note: I also tried minimizing the ligand using OpenBabel, but the same issue persists.

GROMACS version: 2024.2 GROMACS modification: No Here post your question:

I have run MD simulation of a docked membrane protein ligand complex embedded in POPC bilayer through CHARMM GUI and GROMACS for 100ns. My ligand forms a conventional hydrogen bond with LEU182 residue of protein when visualized in Discovery Studio (H-bond distance was 4.57 A). After running the MD Simulation, I visualized the trajectory in VMD, and found the same LEU182 residue interacting with my ligand, along with a few more interactions (cutoff distance: 0.35nm, angle cutoff: 20). But when I calculated H-bond in gmx hbond or gmx hbond-legacy usng the same cutoff, it says, no H-bond found, Ligand doesn’t have any donor or acceptor.

I tried with increasing the distance cutoff (default if 0.35nm in gmx hbond), decreasing the angle cutoff (default is 30 in gmx hbond), even added “nitacc” flag, but still cannot find any H-bond.

I understand there might be differences between VMD and gmx hbond in how they calculate the H-bond, but even after applying same cutoff why there are no H-bond found in gmx hbond?

I am new to using AMBER. My pdb id of the protein is 2beg. Also, in simulating this protein with a ligand, do I need to remove the hydrogen atoms of the complex and protein before running in tleap ? Ligands must have hydrogen atoms which can be added through avogadro?

Your help would mean a lot.

Is it a good idea to try to achieve binding of my protein to a ligand by soaking, even though the Kd of the interaction is in the mM range?

I have many drops with the crystallised apo-protein from the optimisation that form nice single crystals, unfortunately using the same conditions again but with the ligand for co-crystallisation I do not have crystals for all ligands.

Would it be a good idea to test soaking with the native crystals by putting them in the same solution + an excess of ligand (around 50mM)?

Do you have any suggestions?

Hello everyone, I am using Gromacs 2024.2 version of MD simulations and my question is

"When performing MD simulations on a protein-ligand complex involving a cofactor and a substrate, is it necessary to include the cofactor in each simulation for different substrates? How can I effectively isolate and analyze the protein dynamics in a complex with only one ligand (substrate), excluding the cofactor from the resulting trajectories?"

Kindly clarify my question, your help is greatly appreciated.

Thank you

Hello everyone,

I am working on a peptide-protein interaction simulation and I want to extract the RMSD of the interaction as suggested by mdtutorials. Specifically, I need to calculate the RMSD of the heavy atoms of the ligand (peptide) and the backbone of the receptor (protein).

However, when using the “Backbone” selection in GROMACS, it mixes the information from both the peptide and the protein, which is not what I want. I already created an index file where I separated the peptide and protein into different groups, but the problem is that these groups include all atoms from each of the two components, not just the backbone for the receptor and the heavy atoms for the ligand.

How can I modify my index file or selection to only include:

Any suggestions or guidance on how to separate these selections properly for RMSD calculation would be greatly appreciated!

Thanks in advance!

I wanted to do a protein and ligand simulation in GROMACS when I encountered this error, and my force field is CHARMM:

The residues in the chain THR32–HIS369 do not have a consistent type. The first residue has type ‘Protein’, while residue MSE68 is of type ‘Other’. Either there is a mistake in your chain, or it includes nonstandard residue names that have not yet been added to the residuetypes.dat file in the GROMACS library directory. If there are other molecules such as ligands, they should not have the same chain ID as the adjacent protein chain since it’s a separate molecule.

I would be happy to know your opinions and get your advice.

There is a cobalt in active site of protein, I want to use CHARMM36 ff in gromacs I'm no getting how to start. Can anyone suggest me any tutorials or documentation should I follow for performing MDS of metallo-protein with ligand. thank you!

Hello! So i was doing a molecular dynamics simulation between HIV reverse transcriptase (PDB ID: 3LAN) chain A as receptor and a compound called Erisubin F as the ligand

I used a complex i get after doing molecular docking simulation between the two and then i separate them using grep command in gromacs

I already did all the steps (creating topologies, merging topologies of receptor and ligand, ionization, energy minimization, equlibration of temperature and pressure, and production). After production i visualized my simulation result using VMD Chimera, but in the complex the ligand is not present. Can anyone help me determine what is wrong? Thank you

Currently, I’m using Vina to test putative docking sites generated by another program we are testing, our pipeline involves just automating the process of extracting atom coordinates and processing the receptor and ligand files prior to docking.

To speed up processing we use centroid coordinates for the gridbox from the putative ligand position and give an arbitrary size (usually not too much larger than the ligand being tested) For the grid box. My question is if the ligand is longer/bigger than the grid box, how does This affect Vina’s docking?

Attached is a docked result where we used a 20x20x20 grid box from the centroid coordinates (Predicted pose in blue and vina docked pose in pink) what are the conditions the Grid box sets for the docking. are there other ways to test the site without making the search space too large?

I am learning MD simulation using GROMACS, and I need to generate ligand topology using CGenFF. However, it's been two weeks, and I still haven't received verification. Can you suggest other websites or tools for generating ligand topology.

Thanks so mcuh.

Dear friends,

Currently, I am working with MD Simulation with GROMACS 2023 and everything has been going well. Except this one:

When I try the energy minimization with the below commands, such an error occurred

- gmx grompp -f em.mdp -c solv_ions.gro -p topol.top -o em.tpr

- gmx mdrun -v -deffnm em

I tried to increase the box size with the command:

- gmx editconf -f complex.gro -o newbox.gro -bt dodecahedron -d 1.4

But even when I set "-d 10.0", the problem still exists with other residues belong to the ligand so I believe there is a systematic problem with the ligand.

I used CGENFF to generate the "Ligand.str file". It works well in other cases (protein in complex with or without ligand". Also, I view the complex structure with Pymol and Discovery Studio 2021 but do not realize any abnormal sign of the complex, or it is because I do not know how to view correctly to identify errors.

So I am begging for your help, any help is appreciated.

Thank you and best regards.

I use Chimera and AutoDock Vina to process the 3NVY complex. It is clearly stated that molybdenum (Mo) should not be deleted during molecular docking with xanthine oxidase (XO), as it is an essential component of the catalytically active site. Mo plays a crucial role in ligand recognition and enzyme catalysis. Removing it would make docking unrealistic and invalidate the results. However, when I retain the Mo, an error message is displayed. On the other hand, if I remove the Mo and redock to check the validity of the steps, I can't reproduce the interactions of the crystallographic complex. How can I solve this problem?

Hi researchers,

I have downloaded 20,000 compounds from databases in .sdf format in a single file (size: 108 GB).

Could someone guide me on splitting the enormous single ligand file into separate files? In the past, I've used open babel to convert the file from .sdf into .pdb. But, I wish to split this vast database ligand file into separate ligand files for molecular docking. Can I use the Open babel, command prompt for this work? Kindly do give suggestions on this issue.

thanks in advance

Greetings to anyone who reads this question. The problem that I am facing is whenever I try to run Autodock 4.2 and Autodock vina for my compounds that contains Bromine, the error that occurs is, in the poses when visualised through Biovia DS, it prompts that "ligand is not a single fragment" and the Bromine doesn't contains any bonding or interactions. However, on the internet, in several research papers, I have seen simulations run through Autodock, and they have reportedly found the interactions for the compounds that contain halogen especially Bromine as well. Thus, if anyone do knows the solution to this problem, please suggest. It would be much helpful. Thank you.

I have attached a picture of the same where Bromine is identified as a single element after docking. Thank you. Please help.

Does Ni(II) ion bonded with "N" or "S" parts of the organic ligand?

Send me the paper related to this idea.

Hello I would like to ask a question regarding validating my docking results.

So for some context, I was conducting blind docking to Clusterin (7ZET). My issue is that the ligand for it (NAG) does not appear to be inside the binding pocket at least it looks like it to me so I'm not sure if its actually a ligand in the binding pocket or just a random O-GlcNAcylation accidentally labeled as "ligand" (the ligand quality assessment in the RCSB PDB page is also not very great). However I did also conduct hot spot analysis using FTMap which docks a set of fragments into the protein to look for binding sites and I found that the predicted binding site there very closely matched where my actual fragment dataset binded. So my question is can I use my FTMap results as a way of saying it "validated" my docking experiment. I also conducted Consurf analysis which I can further use to bolster the validity since the conserved regions are in agreement with my docking experiment and FTMap analysis.

Hi, i am currently doing my final year project. I am new to docking software and as per what i read, docking involve protein and ligand, and by using docking software i can predict the binding site and binding affinity. Currently, I want to predict the binding site and the affinity between Delphinidin 3-O-Glucoside with metal compound such as AlCl3, KCl, MgCl2 etc. Is it possible to use docking software?

So I am running Maestro Induced Fit Docking, and after completing the task I would like to measure the distances between the interactivo residues and mí ligand, similar to when Docking molecules using ”ligand Docking”. Is therw any way?

thanks

Hi all,

Please suggest how I need to optimize a small molecule to generate the topology file for the ligand to process it for Protein-Ligand MD simulations.

I have tried to balance the valency of the molecule, after which I have submitted the molecule to CGenff server, but the charge penalty and penalty scores were very high.

After which I have tried to optimize the molecule using Avogadro software. Using the output from Avogadro, I have resubmitted the molecule to CGenff server, after which the penalty score was even higher.

I have also tried PRODRG and ATB but the molecule was broken in case of PRODRG, while processing for MD. The molecule contains 1 chlorine atom, also attaching the warning suggested by ATB server.

Kindly suggest how can I process this molecule? I am really new to this work. Please suggest if I am processing it appropriately or not.

Hi

I am trying to perform MLSD to understand the docking interaction of 2 ligands with a receptor at a same time.

Successfully completed the docking in both the method but the result I obtained contains only one ligand.

Kindly help me to rectify this issues

Thanks in advance

I downloaded the ligand file in SDF format from the ZINC database, then converted it into PDB format using OpenBabelGUI. This file was then opened in AutoDock Vina and converted into PDBQT format, and finally, it was docked with the enzyme's active site. After docking in the command prompt and splitting via vina_split.exe, different poses of the ligand in the enzyme's active site were found. When this ligand file is opened in Biovia Discovery Studio for visualizing ligand interactions, I face difficulties with the ligand breaking apart. If anyone can help me resolve this problem, I would be grateful.

Hi everyone, I am using Autodock and I'm fairly new and unskilled in it. I was performing a protein-ligand dock. I prepared the protein and ligand, saved them in pdbqt, prepared the gpf file and set the autogrind.exe and parameter file for running autogrid. But when I click on launch, it doesnt generate the glg and map files.

I'm not sure if this is of context but when I choose my ligand to set map types, it shows me a warning and a python shell errow, both of which I have attached below,

What should I do? Can anyone help me?

What are the purchasable ligand databases which are currently also updated.

I have been looking into Zn purchaseable db through Pharmit server, it is really not updated and the ligands are no longer buyable.

Other than Zn I can think of FDA-approved ones. But are there any other database other that these two, taht has a buyable section?

Thanks

Sanjukta

I analyzed alphafold prediction of receptor and want to docking, previously, I optimized the receptor with openbabel in python but the result wasn't good. I optimized chemical ligand and want to start protein- ligand docking with MD and how to start?

Hello RG Forum, towards the above topic, I am running the Orca Command: (base) Joels-MacBook-Air:14C-DON-C8i joelsubach$ orca 14C-DON-C8i.inp > 14C-DON-C8i.output.out (in this case DON means donor) to generate the above output.out file which will be subsequently used towards a VMD ffTK Charge Optimization. The above C8i .inp File exhibits a -2 Charge via its two negatively-charged carboxylate ion COO- groups generated via an Avogadro pH of 7.4 (prior the ligand exhibited instead two carboxyl group COOH groups (see screenshot attached via Dropbox Link below, figure labeled Charge-2.) I had successfully executed the above command for several other .inp files within this structure with this -2 charge within the respective .inp files, however, this C8i.inp file seems to be generating a fly-away at this proper -2 charge but when I change the C8i.inp file to a 0-charge (C8.inp) the orca command successfully generates the proper water optimization distance (see screenshots C8i_FlyAway and C8 respectively also within below Dropbox Link). Accordingly my inquiry, may I in this instance use the 0-charged .inp file exhibiting the proper water displacement out.out file or must I resolve this issue within the structure i.e. the ffTK Manual states: `Cases in which water molecules appear to settle at large distances or even “fly away”, indicate the absence of the expected minimum for the given interaction site. This can be due to improperly defined interaction type (donor vs. acceptor), secondary interactions (usually steric clashes) that destabilize the water interaction, or simply an unfavorable environment due to the local electronic structure. Observations from visual inspection can be used to troubleshoot the input settings or exclude particular target data from the optimization´.

Maybe an Orca charge adjustment of 0 is needed to modify steric clashes and or an unfavorable environment, any insight would be appreciated, thanks:) Joel 🚀

I am interested in in silico studies that perform a comprehensive comparative analysis. Ideally, these studies should include detailed docking simulations to compare binding affinities of the modified and original ligands, as well as molecular dynamics simulations to assess stability and binding interactions over time.

Additionally, I’m looking for papers that discuss the synthetic feasibility of these modifications, integrating both binding and synthetic analyses into the evaluation.

Hi,

I have a problem. The two residues in the protein structure are not connected, which causes the short section to appear separate from the protein. This results in a visible gap in the RMSD and RMSF graphs.

I predicted a protein with high confidence. I tried to replace the ligand where it was, but it was not exactly where I wanted it. That's why I want to use the original X-ray one. How can I prevent it from appearing as a gap in the RMSD and RMSF graph? After all, this is a matter of the stability of the complex.

A software that can be downloaded or available freely for students.

Here, a ligand search is done to get the CGENFF force field for serotonin. But the atom type is mismatched.

I have synthesized a series of organic compounds that can bind with anions. I have the single crystal of the ligand. now, the obstacle is that my synthesized ligand is neutral and it can bind with an anion. Now, if I want to optimize the structure of the compound after binding with anion then how should I consider the charge of the compound? precisely, for an example, during DFT calculation for a metal complex, if the complex is neutral we give the charge o as input for our complex, and if the complex has an uncoordinated anion to neutralize the overall charge and we aim to optimize the complex only in that case we put +1 charge as input.

My question is, what will be the charge in the input file for my compound after binding with anion/s? Should I consider the whole molecule as a neutral or—ve-charged species?

Respected Sir/Madam, please help me to figure out this problem

Hello everyone.

In my project, I am dealing with a siderophore binding protein and I need to calculate the dissociation constant of the protein with various siderophores and its precursors with and without the iron ion.

Even though I thoroughly dialyzed the protein and dissolved the required ligand compounds with the dialysis buffer, I got a signal like this when conducting ITC with Fe-siderophore.

I am pretty sure the ligand itself does not bother since bare ligand was also conducted and it did not make any problem, but I used FeCl3 anhydrous for adding Fe ion into the ligand.

So I wonder whether Cl- ion was too much (I applied [FeCl3] to have the final concentration to be ~100 mM) or something else.

I synthesized Co(II) triazole Schiff base complex using Co(II) acetate tetrahydrate in 2:1 ratio (L:M). The ligand is synthesized from 3-amino-5-mercapto-1,2,4-triazole with benzaldehyde derivative. I stirred together the cobalt salt with the Schiff base for 4 hours at room temperature. Filtered the precipitate and washed with etoh. After dried, tested for every solvents but only dissolve partially in dmso.

Then, I tried to dissolve it in dilute HCl. It completely dissolved and gives a light orange color, after I added acetone and mixed it together, it gives a light blue color.

What is happening with the cobalt complex?

Hello,

I am trying to use the BioTek Synergy HT instrument running run Gen5 3.1? software. I have done polarization in the past but am unfamiliar with this machine and software. Any help/guidance would be greatly appreciated.

I am trying to do a reproduce a binding assay with fluorescent ligand and protein. I have used the concentration of protein and ligand that I have used for an ISS OC

spectrofluorometer (ISS, INC. Champaign, IL). Any thoughts?

Thank you for your input,

Sean

I performed post-MD MMGBSA for one of my best active compounds (IC50: 2 nM).

But the ΔG value is positive.

What can be the reason?

a. Is the MD simulation time not sufficient? (But the ligand is almost stable after 300 ns)

b. Am I choosing the wrong binding site?

c. Should I try with MMPBSA or normal mode instead?

d. Is the initial starting ligand pose not OK?

When I process the ligand in AutoDock Tools, the rotatable parts of the chemical structure disappear after I save it in PDBQT format. I have uninstalled and reinstalled the program, and tried versions 1.5.6 and 1.5.7, but the issue persists. I am an AMD user and cannot perform docking with the ligand's rotatable bonds. However, if I remove the rotations, I can perform the docking normally. How can I solve this problem?

I have performed 200ns simulation of the protein ligand complex using Schrodinger Desmond .

My story is that I want to predict that my ligand causes the conformational change and dissociate or destabilize the chains of protein .

My protein has two chains A and B in total 805 amino acids , I have docked the compound on site as mentioned per literature it shows -5.9 to -7.2kcal per mol docking score on site as mentioned in literature

Then I make a complex of best pose on ligand , what I want to discuss that I want that binding of ligand on chain A doesn't effect on stability of protein but binding of ligand on chain B or at Interface could produce the big chain on conformation of protein as well as stability and dissociate them .

That I want , the ligand as proved such mechanism in invitro studies.

I am attaching the results the RMSD of protein and ligand was stable in begining but suddenly it hits up 50A.

The question is that if the protein rmsd is so high so it could create effect on ligand Rmsd or not and if ligand rmsd is high and I want instability so it would be acceptable or not .

I have performed the apo system simulation also it shows Rmsd less than 4A and fluctuations are less .

In comparison with ligand the system was highly unstable .

So how I will present my results because most simulation are done to check stability but here I want instability of protein protein Interaction after ligand attachment to chain B to any part of it or at Interface even reaching to chain

I have also calculated the distance of main amino acids needed for stabilization of protein there distance also increase very much .and fluctuations are more also .

In conclusion I want instability in protein after ligand attachment .

Kindly discuss in detail any one with generous comments.

Thanks .

Hello RG Community I hope your well:),

towards the above topic, I have generated 10 ligand 3-D Conformational Structures via a SMILES within PubChem, there are no PDB Images yet for this ligand-protein complex. My Aim is to dock this ligand to the protein, where each docking would generate 9-models ultimately generating 90-docked models in total.

All of the SDF Downloaded Coordinates of the 10 ligands exhibit similar energies and subsequent to visualizing 9-models generated via the first ligand docking, all models exhibited similar docking energies, similar amounts of hydrogen bonds and other bonds and similar visuals.

To manage time is there a way to critically select one of the conformations amongst the others nine?

Similarly is there a critical way to choose one of the models generated amongst the remaining 8 models generated?

(I think in this case due to the lack of experimental evidence, this would be trial and error based.)

And I have elected the PubChem over other website Smiles to 3-D Conformational generators due to their more in depth algorithms, would you agree that PubChem would be amongst the top-rated 3-D conformational generators?

Thanks if you have any suggestions:),

Joel 🚀

Hi all,

I recently performed a antibody-antigen affinity test using Fortebio Octet.

The format is as follows:

Antigen was captured by SA sensor then interacted with VHHs. Double reference was applied. But there is negative signal when the reference sensor(no ligand on it) dipped into the well of analytes except the buffer well.

The blue curve is the buffer and the other two are analytes with two concentrations.

Can anyone give me some suggestions on it?

Many thanks!

I have tried many times to dock ubenimex n (Compound CID: 72172) with a protein but every time the ligand breaks into two pieces. Kindly help. i have used chemdraw, 3d sdf file, gaussian fchk file, mol2 file to convert the ligand into pdb file but every time Autodock splits the ligand. Hydrogens and charges were added. ligand is neutral.

Hi. I'm analyzing the kinetics of antibody antigen interaction. I have some that show very low Koff. The problem is in the dissociation phase the curve is not only stationary but increase....the reviewer need explanation. Is a question of normalization with the base-line? I mean there are not many things I can have done a wrong

in the experiment. Please I need a acceptable justification.

Hello.

I am trying to parametrize a ligand using SwissParam. It generated me topology (.rtf) and parameter (.prm) files, but the topology file isn't working in Autopsf so I can't generate a .psf file for my future NAMD simulation.

Below is the topology file, mol2, and the prm. My assumption is that the ligand has atoms not supported by the CHARMM force field.

I am conducting a molecular docking study using peptides as ligands. I successfully ran the docking process using autodock vina, and when I viewed it using Discovery Studio, I realized that the ligand have missing bonds. I retracked my process and found out that the pdbqt file of my ligand is the problem. Here is a screenshot of my pdbqt file of my peptide, IF in DS. Attached also is the pdbqt file of my peptide.

Please help me on what to do.

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?

I have performed multiple ligand molecular docking using AutoDock Vina in windows. There is any way to extract lowest binding energy value from all log files rather than copying value by opening each file one by one?

I am trying to see whether there is an interaction between a specific virus protein and a natural compound (which will serve as my ligand), however I have no experience in molecular docking. I am aware that there are certain steps that need to be undertaken for me to get my protein and ligand both ready before I run molecular docking, but I am not sure where to start or how.

Some guidance would be very much appreciated. Thank you in advance.

Hello everyone,

How can I prepare a hydrophobic ligand for molecular docking? Is there any tool for hydrophobic ligands?

I am trying to dock a small ligand into a protein containing three Mg2+ ions that are essential for ligand binding using AutoDock Vina. However, when I prepared the receptor pdbqt file via the Autodock tool, the charge of Mg2+ was zero. Can you guide me on how to address this problem? Thank you so much.

I have done molecular docking for 70 pdb comprises 30 pdb with ligand and 40 pdb without ligand against 418 ligand compounds from Drugbank. So, for each pdb, there are 70 different results for each 70 pdb. So, how can I visualize the interaction for each pdb against 418 ligands automatically by using Biovia Discovery Studio without manual method? The criteria that I am looking for are the position of ligand inside the binding site and the 2D diagram interaction.

Dear Researchers kindly suggest a molecular docking online free web server that does not involve protein + ligand but it should be for ligand + receptor. For example: patch dock web server. Thanks in advance

Dear scientists, I need help with molecular docking with Autodock.

- When I upload the Protein or Ligand structure, the command "swig/python detected a memory leak of type 'BHtree *', no destructor found" appears on the screen (Picture 1).

- Then, I can't Run AutoGrid or AutoDock. When I press the Launch command (with files created), it only results in a window like this and sometimes nothing happens and The error log says "Sorry, I can't find or open Grid Parameter File "C:/Users/..." . I have everything in one folder already so it should find the files (Picture 2).

Can anyone tell me what have I done wrong and how to correct it? I tried a few times and it is still the same.

I look forward to receiving help from you.

Thanks very much.

I have performed the Molecular Docking using ADFR suite, I have obtained the files in _out.pdbqt format for ligand docked poses, upon inspection, both visually and reading the pdbqt files of ligand, I have found that there are flexible residues of protein present in ligand docked pose. Now I want to make the complex of the docked pose with the protein structure to go for MD simulation, however, I am not sure how to do that as the rigid receptor file of the protein also contains the residues which are present in the ligand file. If anyone knows how can I combine the ligand and protein file into a single complex so that the flexible residues position from the ligand file can get appened/fixed in protein structure so I do not get double same residues in the complex. Kindly let me know. If any more information is required, I am also happy to provide more details about that.

After the adsorption of the drug (LFV) from the wastewater, my LDH(Ni, Co, Al)/ CS composite exhibits a new peak in conjunction with the Al reference peak (73) at 68 eV. Is there a correlation between the occurrence of the second peak and the interaction between the ligand and the metal? (LMCT), (MLCT)

Hi everybody,

I would be grateful if someone could give me some suggestions on how to properly fit binding data, in particular using the Hill equation.

I often use biophysical techniques (e.g. SPR, FP, etc.) to quantify protein-protein interactions. In several cases, it happened to me that the data could not be easily fitted by the classical "1:1 binding" model. In particular, when experimental points lie on a steep sigmoidal curve, I used the Hill equation to fit my data, but this raised some doubts to me.

- First, could the Hill equation account for biological phenomena other that binding cooperativity (e.g. ligand heterogeneity)? Otherwise, are there better models to be used in those cases in which no cooperativity is expected?

- Second, in the Hill equation F=(c^h)/(c^h + k_A^h) [F is fractional occupancy of binding sites; c is the concentration of ligand, k_A is the half-maximal ligand concentration and h is the Hill coefficient], the dissociation constant (K_d) corresponds to k_A^h . Since this is a power function of concentration, the unit by which concentration is expressed heavily impacts on the fitting value of K_d. How should concentrations be expressed?

Thanks in advance to anyone that could give me some hints.

Best,

Filippo

Hello good people, I'm trying to do a simulation with my siRNA (as a ligand) and Ago-2 protein. I build my siRNA structure using mFOLD, RNAComposer, and the protein using the Swiss model webserver. Also, I've performed the simulation in Desmond. However, the problem has been arising after loading the output file. There is no ligand with protein in the result pdf. What do you think I should do now? Please help me.

I was trying to get the OPLS-AA parameters for an organic molecule, actonitrile (CH3CN), from LigParGen using PDB as well as smiles code ("CC#N") .

In case of PDB I found the error: " Found residue ligand N".

In case of smles code, I encountered the error, "Sorry, an error has been detected in your input data (file, smile or selected charge): export BOSSdir=/var/www/html/ligpargen/apps/boss-4.9;/var/www/html/ligpargen/apps/anaconda2/bin/python2.7 /var/www/html/ligpargen/apps/ligpargenCode/Converter.py -s 'CC#N' -r UNK -o 0 -c 0 > /tmp/errorServer.log Problem found in the file format. Please, check the input file. In case you are not able to find the error we suggests to use the SMILE code".

Please suggest me so that I can get the OPLS_AA parameters for acetonitrile with 1.14*CM1A-LBCC charge model.

I need help with docking a fatty acid and insulin receptor IR3, I have tried the docking and got an reference RMSD value of 38.59 and binding energy of -3.39. The exact step I have followed is

Adding Polar Hydrogen - Adding Kollmann Charges -Write PDB - Open Ligand -Detect root - Choose root - Save Ligand - Grid - Choose Macromolecule - Choose Ligand - Grid Box - Save gpf - Running Autogrid - Running Autodock using Genetic Algorithm and Lamarckian Algorithm

I have also tried minimizing the energy of the fatty acid using Avagadro.

Kindly help.

Autodock vina just provides binding affinity and docked protein and ligand .when their interaction start off and view data table on biovia discovery studio,no information about inhibition constant, reference arms bond distance, intermolecular energy are found. How to find these information for autodock with vina.

why don't d-orbitals split themselves because of themselves without the presence of ligands? Electrons are indistinguishable. Why wouldn't it be more correct that protons from a ligand split the d-orbitals rather than the lone-pairs cause d-orbital splitting energy?​

Good afternoon!

I am new to molecular docking. I have watched lessons on youtube, read forums, but still have questions about the algorithm of the work. I hope to find answers here. Sequence of work in AutoDock4: 1. protein preparation 2. ligand preparation 3. gridbox construction 4. map calculation 5. docking calculation 6. analysis In tutorial of molecular docking on known systems is considered. We know in advance where ligand binds to the protein. But what is the step-by-step algorithm of non-directed docking? And I have no prior knowledge. I think I need to create a gridbox as large as possible (126x126x126, 1 A). If the protein does not fit entirely in the gridbox, then move the center of the gridbox so as to capture the entire structure. That is, at the first step of molecular docking I will have several gridboxes created and calculated. Then I will gradually refine the gridbox values. For example, the next step will be for 126x126x126, 0.375 A maps. And so repeat until the map reaches a size, for example, 50x50x50 0.375A. And if my thoughts are correct, this is where my questions arise. 1. Should the maps overlap with each other in order to cover the whole space? 2. How should I decide which regions of my protein is less favorable? So I can further forget about them and focus only on the most favorable? I look forward to your answers and recommendations. Thank you in advance!

I'm guessing it's because the ligand experiences too much electron repulsion or proton repulsion from the chromium to insert them close to the 3d-orbitals which are close to the metal nucleus. Is that correct?

I have been trying several methods to parameterize the acetyl Coa ligand using both the web-based i.e charmm gui, playmolecule, cgenff method and antechamber method of Amber. The ligand parameterizations fail due to unrecognized atom types. Due to this, I am not able to build the system. Can anyone help me with this?

I have done docking and molecular dynamics simulation of two wild-type and mutant enzymes with ligands separately. To revise the article, the Reviewer has left this comment to get the contact maps analysis. How should I do this? Is contact maps analysis for the interaction between enzyme and ligand?

Reviewer :

I recommend the authors to provide the essential dynamics analysis such as Gibbs free energy, contact maps and refer the above mentioned articles for the similar analysis. These analyses provide more insights for structural based studies.

Thank you

Hello,, The metal complex ligand appears incomplete in the screen of the discovery studio visualizer

Good day,

I am a student trying to work on Autodock for a project regarding Ligand-DNA interaction so i am quite new to molecular docking. i have followed tutorials and did all the steps recommended for the docking to work with PDBQT files for both the ligand and DNA, but every time i run AutoGrid the window for the process opens for less than 1 second and then shuts down immediately with no output file. i made sure the previous steps were working correctly and to open the ligand and DNA files in their respective input category and the paths for each part in the run window right before the launch have no spaces and are correct. Same problem happens with Autodock.

Does anyone know if there is a fix for this problem?

Thank you in advance.

I have been performing Molecular Dynamic simulation. While calculating RMSD trajectory for protein and protein + Ligand, there is sudden increase in the trajectory tools. What could be possible reason. I have attached two files here.

I have done docking and molecular dynamics simulation of two wild-type and mutant enzymes with ligands separately. To revise the article, the Reviewer has left this comment to get the contact maps analysis. How should I do this? Is contact maps analysis for the interaction between enzyme and ligand?

I am performing fluorescence experiments using a ligand to detect metal ions. I want to determine the Lowest Detection Limit (LOD) using the formula LOD = 3σ / K. However, I'm uncertain about determining σ, the standard deviation. In my experiments, I varied the concentration of the ligand and measured the resulting fluorescence intensities. I then plotted these values to calculate the standard deviation. Could you please confirm if this approach is correct?

Hi! I am currently working on a protein where I have selected residues within 10A of its bound ligand in pymol. However, I can not find a way to print out what residues are contained in that group of residues that are within 10A. So far, I have tried this:

However, after cross-referencing the residues printed with those that I can see selected in the pdb file sequence, this method omits many of the residues.

Does anyone have a pymol command line they have used to accomplish this!

Thank you,

Kat Myers

I have been able to assign the CHARMM forcefield to my ligand i.e. acetyl coenzyme A but not the amber forcefield. I want to run amber forcefield and the parameterization of ligand is failing. I am also attaching the structure of the complex to which I want to assign the amber forcefield. Kindly, someone help me with this.

During the preparation of a ligand molecule in autodock or openbabel Cl atom is not showing in the .pdbqt file whereas it was present in the pdb and sdf file. Due to this Cl atom is not showing in the docked complex as well. How do we resolve this issue? I am attaching two images for your reference.

Thanks in advance