Questions related to Ligand
Hello, I've recently started exploring molecular docking applications, and I'm still in the early stages. I'd like to ask Can I choose a ligand by giving the amino acid sequence and then do docking? Which applications would you suggest?
I am calculating the oniom energy for a complex, receptor only and ligand only to calculate the free binding energy of the ligand of interest. I've seen different papers that do get similar kcal/mol calculations to their respective docking experiments but wanted an opinion on if it truly makes sense to do so. Both methods are taking in completely different things when forming their calculations. I figured each would only be able to be compared relative to each other? Example. Ligands can only be compared to each other via docking alone and ligands used in oniom can only be compared to each other through oniom.
There is a large protein that I would dock a file containing 3 different ligands with to see if distinct binding sites are filled or not. Is any software to do so?
they are seemingly limited to one ligand docking
Thank you in advance
I was performing free energy calculation using g_mmpbsa tools. From the summary data i got the value of binding energy, but when i check the output file, it shows only data energy for the complex. Meanwhile we need to calculate the energy component of protein, ligand, and protein-ligand complex to get the binding free energy. so is that means that we have to perform the calculation for protein, ligand, and complex separately?
I'm working with a protein that does not have a co-crystallized ligand. How to analyze the best docking pose and validate the docking procedure?
I created a grid using the Autodock tools and then using those coordinates and size I created a configuration file for Vina. But in the results, the location of the ligand do not match the specified coordinates and size. I used the PyMol for visualization, but the ligand is not placed within the previously selected coordinates.
Thank you for help.
Dear Researchers and Scientists, I would like to know the molecular mechanism behind Cancer-Cell-Specific Nuclear-Targeted Drug Delivery.?
Please suggest any appropriate ligand except hormones
Is it possible to target cell nuclei with amphiphilic lipids or catatonic lipids? If “yes,” please brief the molecular mechanism.?
Some research articles read and found it could be possible by Vitamins-A but no clear evidence about molecular mechanism.
I am looking for a binding ligand that will easily bind with a nucleus receptor-like Type I Nuclear Receptors or Type II Nuclear Receptors.
I am studying protein-protein interactions and from MST, I observed the binding during binding check but I cannot get a full saturation anywhere with binding affinity tests. I tried changing the ligand concentrations but did not make any difference. Can someone explain to me the possible reasons for this type of behavior or what I can do to improve that? I have attached the picture as well to have an idea.
I am trying to dock a planar ligand with a receptor molecule using Autodock tool. I want to freeze the torsions of the ligand. So, I changed the number of active torsions to 0. Also, in the .dpf file I set 'torsdof' to 0. However, I'm encountering issues with this approach.
I would greatly appreciate any insights or suggestions regarding this matter.
We have to perform MD simulations on a limited number of protein:ligand complexes.
Since we aren't MD specialists we are trying to use charmm-gui.org to make the work easier.
The input pdb file contains protein + ligand coordinates. We have produced a .mol2 file using https://www.cheminfo.org/Chemistry/Cheminformatics/FormatConverter/index.html
We also saw that sometimes there are problems with .mol2 files and there is a script that may solve these problems (sort_mol2_bonds.pl).
When running charmm-gui , Solution Builder, then the program fails every time at the stage of generate.pdb with this error message (whichever of the two .mol2 files is used, either coming out of OpenBabel or after running the sort_mol2_bonds.pl) : "skipped empty mol2 file".
The mol2 files we are using are not empty.
Hence the questions are: is charmm-gui broken somehow? Or is there a solution to this problem allowing us to perform MD simulations on these protein:ligand complexes?
Thanks in advance.
I am doing a titration of ligand into protein and am getting good heat releases compared to my ligand into buffer.
I am getting more heat release in later injections. Could cooperativity explain this because I have used varying concentrations of protein and ligand and get the same curve.
So I am currently titrating a ligand (A, 12 µM) which is a dimer (in syringe) to a monomeric protein in cell (B, 61 µM). The experimental conditions are 20 mM Sodium Phosphate, 100 mM NaCl, and 2 mM TCEP at 20 C. I observe reasonable heat change after titration but the stoichiometry is consistently lower than 1. Though on the literature, I have observed a N~1 for the same binding proteins (though the titrations are done in reverse orientation).
I believe it is due to the low C value that I am not observing a sigmoidal binding curve. Unfortunately, I am limited by protein and can not further increase the concentration without precipitation of my protein. the
Would a low N value mean only a fraction of my protein in the cell are binding competent/active? If so is there any way to diagnose using any other method and correct it? Below are the attached thermograms and binding isotherm for more clarity.
I want to perform a protein-ligand MD simulation using Amber. I have generated ligand frcmod, lib, rst7, and prmtop files. Then, I loaded my complex file, which contained the ligand and protein in water (generated using Packmol-memgen). However, when I tried to save the rst7 and prmtop files for the complex, I encountered this error: 'FATAL: Atom .R<***> does not have a type.' I've attempted to resolve this issue multiple times, but it keeps happening. I followed the tutorial exactly as outlined on the AmberMD website ('Simulating a pharmaceutical compound using Antechamber and the Generalized Amber Force Field'). Surprisingly, the problem persists. even though I tried to use the same molecule, protein, and files provided on the website to check out if there were any problem with my own files and again i ended up with same problem. Can anyone help me figure this out?"
The molecular docking was performed by redocking the co-crystallized ligand and validating the protocol by finding the RMSD of the docked ligand by superimposing it on co-crystalized ligand. Afterwards the docking was performed on new set of ligand library. But can we justify the results of docking without doing md simulations? If yes, then please provide a reference from article.
When ligands are dissolved in a copper (II) solution with a ratio of 2:1 (ligands: ions), how can one identify the oxidation state of the complex? Also, if NaOH is used as a pH controller, what will be the interaction between the OH- and the complex that was just formed? Will the OH- itself become a ligand (create a new complex) and in this case can the whole complex be later reduced using a reductant? It can be seen that most research conducted at the moment used a pH control threshold above 11 before reducing the copper. Why does it need to be above 11? What is the mechanism behind raising the pH to 11?
I was trying redock a ligand to a protein, which was already present in the PDB crystal structure. I extracted the ligand and tried to dock it again using Autodock vina in that same site specified by a grid box centered on the original position of the ligand and of size 30x30x30. The original docking mode in the crystal structure had 4 H-bonds, but the vina docking result has only one, and that too in a different position, about 10 A from the original position. I am trying it with different gridbox dimensions, with different exhaustiveness values (8, 32), but every time it is getting docked at that wrong position. It should also be noted that the docking results themselves are very consistent among themselves. (Refer to the attached image. Blue: Original position with 4 H bonds, Pink: Vina docked position with only 1 H bond)
Why is this happening? How do I get the correct docked structure? Is this a problem with vina itself, that it is not being able to find the correct docked position? If so, then is there any better tool for docking?
Hydrogens are being added to a receptor protein in order to fix it structure, but is it necessary to do the same to a ligand molecule?
Hello fellow researchers,
I made a docking from one of the articles. This work was done as a practice and to ensure the correct process of doing the work. When the docking was done and I checked the result of my docking with the same article, my results were different from that article in some ways, although I must say that I had to change the settings in several steps and optimize the ligand. My question is, is the difference (although close) of the results normal and not a problem? Thanks.
I have a question with the results that you obtain in RMSD calculation. The Y-axis values are between 30-50 (Amstrong?) and I had read that a good RMSD value is between 1-2,5 amstrong. But when I visualise in VMD my molecular dynamics, the ligand remains bound to the protein at all times. So my question is: Is a high RMSD related to the fact that my ligand is far away from the protein? Is my ligand far away from the active site but it is bound to another part of the protein? Or do I have to change the simulation parameters because the simulation is not well done?
Thanks in advance
We have used CaFE Software to predict the binding free energy of our protein-ligand complexes from our molecular dynamics simulations.
Fortunately the Software has run successfully however don’t know the exact meaning of the physical thermodynamic parameters calculated: a) Complex total (kcal/mol), b) Receptor (kcal/mol), c) Ligand (kcal/mol) and d) Delta (kcal/mol).
We understand that the first value “Complex” can be interpreted as the binding free of the protein-ligand complex , However, we are bit confused about the last two terms “Ligand” (c) and Delta (d) what would be the difference between them? or which is the most important parameter to determine the binding free energy of the ligand to the receptor, is that (c) or (d) parameter?
Thanks in advance and best regards,
I am trying to dock a ligand on PyMol using the DockingPie plugin. When I import the ligand as a pdbqt file on pymol, DockingPie gives me the option to import that ligand for docking later on. However, when I select "set ligand" in the DockingPie plugin, I receive an error stating "FileNotFoundError: [WinError 2] The system cannot find the file specified: '01_tclcactvs000ksOway_ADFR.pdbqt' -> '01_01-tclcactvs000ksOway-ADFR_ADFR.pdbqt'"
How do I go about this? Thank you!
I have a question: Does the sensorgram of the negative response look like the attached figure? I use a CM5 chip immobilised with His to capture my protein and then use other proteins as my ligand. The assay is to calculate EC50 and relative potency. My ligands are heat-treated. I would to check if it is normal to not see the capture curve on the sensorgram of treated samples. I have used a control (non-treated samples) and the curves look pretty (positive RU). My samples are at nanomolar concentration (serial dilution) and I use HBS-EP+ buffer.
This message is pooping up despite i am having the grid gpf file in the same folder where i am doing the docking and i have followed all the steps correctly from protein(BSA) preparation to ligand preparation(Ketoprofen). Still I am not able to run the autogrid command. While the same thing i have done for another set of protein and ligand and it worked.
Suppose I have done docking of BSA with Ketoprofen and I have got some poses. I have selected the best suitable pose of the ligand and then I saved that complex of BSA with Ketoprofen. Now what i want to do is that I want to dock the whole complex with another ligand, i.e. now my complex is the new receptor. So if anyone knows how to do it plz tell me
I cannot fully understand the plot attached.Why did I get the negative response value?Does it mean that the ligand is unstable and degradting from the chip surface?
Besides,what does the binding stability plot mean? Should I get a increasing scattering plot as the concentration increases?
I would like to explain a candidate ligand (e.g, small molecule) binding to a targeted protein. As there is no comparison with other ligands, how can we explain that?
Do they have a standard cut-off for free energy binding? Or can we show H-bond interaction from the best pose of ligand and a targeted protein?
Could anyone shed some light, please?
All the best,
I am trying to perform MLSD to understand the docking interaction of 2 ligands with a receptor at a same time.
- For that I have followed AutoDock4 (10.1016/j.compbiolchem.2015.09.008 ; 10.1016/j.biochi.2018.10.007) in that "dpf" has to be generated individually and merge together
- Also I have followed AutoDock Vina (https://autodock-vina.readthedocs.io/en/latest/docking_multiple_ligands.html) with the given scripts
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 am trying to perform simulation of my protein-ligand complex system following Gromacs Protein-Ligand complex tutorial , so during the NVT equilibration using the command
" gmx grompp -f nvt.mdp -c em.gro -r em.gro -p topol.top -n index.ndx -o nvt.tpr"
iI encountered an error
Condition: ip.constr.dA > 0
We should only have positive constraint lengths here"
i am using gmx version 2022
enclosing nvt.mdp input file
how to solve this error ?
I am studying a protein and ligand interaction using autodock4.2, I have a large dataset where I need to study around 15–20 ligands with my protein of interest I have generated 50 different conformations for each ligand using autodock 4.2. Using discover studio I have generated 2D plots, having a huge data set and low time I want to perform statistic to understand the probability of highest interacting residues.
I have attached a plot as an example, can anyone help me out, how to generate such statistics
I am having trouble with my autodock4 after creating modified docking parameter files, when i run; autodock4 -p ligand_HYDRO_protein.dpf -l ligand_HYDRO_protein.dlg
i get this errer;
autodock4: I'm sorry; I can't find or open "protein.F.map"
autodock4: FATAL ERROR: autodock4: I'm sorry; I can't find or open "protein.F.map"
What am i missing?
I have been trying to create a complex for MD simulation in gromacs of Calcium sensing receptor venus fly trap domain with tryptophan in the binding site as it is part of the crystal structure. However, there is an OXT terminal oxygen which CHARMM 36 does not read and a nitrogen atom N that OPLS-AA gives an error for.
I am stumped. I tried using the CHARMM-GUI to create the ligand files for gromacs but it also has an OXT oxygen atom. I used the bound ligand as well as a fresh ligand from pubchem, the problem remains that it is not recognised by Charmm ff.
Please let me know how to prepare my complex?
My desired ligand only has 2d structure there is no 3d structure. So whenever I tried to get 2d interaction ligand is not a single fragment occur after docking. So I converted my 2 d structure to 3d by avogadro and then docked but it keeps on appearing. Can anyone plz help me with this how to solve it
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
I am facing a issue with complex visualisation in ligplot and pymol..
When I tried to open the docked PL complex in the aforementioned tools only ligands are visible and no interaction are visible...While quite satisfaction y interaction are observed when I assessed same PL file in Discovery studio . Please help me to overcome this problem
I have docked several ligand and protein and few of them have an unfavorable bump interaction. When we dock protein and ligand in Autodock-vina, they give us several output like out_ligand_1, out_ligand_2, out_ligand_3, etc.
In my case, for the same ligand but different pose (different output 'out_ligand_x'), one of them has unfavorable bump interaction, and the others don't. But i chose output ligand based on the lowest binding affinity, and that one is the one that has unfavorable bump interaction. My actual question is, is it still valid if I continue the simulation despite of the unfavorable bump situation?
I wish anyone can give me an understanding explanation. Thank you in advance!
I know that if the affinity is too low, assays such as ELISA would not be appropriate, because the off rate of the ligand would be so fast that it would not hold on for the 2-3 hours that it takes to run the ELISA. Does anyone know at what Kd ELISA stops being an appropriate assay?
I have been running ELISAs to determine Kd for an interaction. For some interactions, the Kd, as calculated from the curve by Graphpad Prism, is 300 nM. Is that Kd so high that an ELISA theoretically should not work?
A micellar solution of protein (in PBS, pH 7.4) was loaded into the sample cell of the calorimeter. The ligand was prepared in 10% DMSO and was loaded in the injector-stirrer syringe.
I have also performed a control experiment to consider the heat of dilution of the ligand solution. A similar addition of the ligand solution was performed under the same experimental conditions keeping PBS in the sample cell. Before evaluating the data, the control data were subtracted from the actual experimental data.
N = 0.4
Model: One set of sites
I have few confusions about the pulling code in gromacs, I was using NAMD before and the method was quite straighforward in NAMD to pull the ligand out of the protein, in gromacs it is also straight forward but I need to clear few things
1. In NAMD one can define the pulling direction by using SMDDir in the input file. Difference between the COM distance of SMD atom and fixed atom gives the pulling direction, SMD atoms are usually the heavy atoms of the ligand whereas the CA backbone of the protein is kept fixed. This difference between the COM distances of both tells the pulling direction of the ligand in NAMD in case one does not know the pulling direction of the ligand. Is pull-coord1-vec is same as NAMD SMDDir ? And in NAMD you define the SMD atoms and fixed atoms, here in Gromacs I am confused how it defines the fixed atoms or reference atom which is protein from where ligand has to be pulled out?
I followed the umbrella sampling tutorial in Gromacs
2. Secondly I did few tests regrading pulling out the ligand from the protein using the pull code as below, this is just a test code to understand things thats why applied quite fast velocity.
; Pull code
pull = yes
pull_ncoords = 1 ; only one reaction coordinate
pull_ngroups = 2 ; two groups defining one reaction coordinate
pull_group1_name = Ligand
pull_group2_name = Protein
pull_coord1_type = umbrella ; harmonic potential
pull_coord1_geometry = distance ;
pull-coord1-vec = -0.49 -0.85 0.16 ;
; pull-coord1-origin = 53.12 52.96 53.066
pull_coord1_dim = Y Y Y ;
pull_coord1_groups = 1 2 ;
pull-pbc-ref-prev-step-com = YES
pull-group1-pbcatom = 0
;pull-group2-pbcatom = 0
pull_coord1_start = yes ; define initial COM distance > 0
pull_coord1_rate = 0.01 ; 0.0004 nm per ps
pull_coord1_k = 600 ; kJ mol^-1 nm^-2
I changed one parameter of the pulling code every time to see whether there is any affect on the pulling but by visualizing the trajectories I didn't see any difference, the ligand is still coming out even if I switch off pull-coord1-vec, pull_coord1_dim together. Also with these feature if I changed distance to direction still the ligand comes out.
Secondly if I just keep pull_coord1_dim Y Y Y in all three dimensions it still takes the ligand out of the protein in almost similair direction as given by pull-coord1-vec, if I dont give pull-coord1 vec and only give pull coord1 dim Y Y Y will my ligand be pulled in a random direction?
Also What is pull-coord1-origin? is it the origin of the box?
Anyone kindly let me know what changes should I make in the above given code where I just want my ligand to come out of the protein in a random pulling direction or by the method of NAMD SMDDir?
I am mostly interested in the pulling forces required to pull the ligand, so what should be the pulling code input in gromacs for that?
Thank you in advance, your answer will help me in understanding the pulling code and applying it to my work!!
During the gromacs 2023.1 multiple ligand simulation , I have some problems and constraints in the simulation. In the experiments, I used AMBER99sb forcefield.
How to perform multiple ligand simulations
Whether i have to make different topology files for different ligands? because when trying to simulate at the ionization stage to get the ions.tpr file an error occurs as below:
gmx grompp -f ions.mdp -c solv.gro -p topol.top -o ions.tpr
Ignoring obsolete mdp entry 'title'
Ignoring obsolete mdp entry 'ns_type'
NOTE 1 [file ions.mdp]:
With Verlet lists the optimal nstlist is >= 10, with GPUs >= 20. Note
that with the Verlet scheme, nstlist has no effect on the accuracy of
Setting the LD random seed to 2095054833
Generated 3486 of the 3486 non-bonded parameter combinations
Generating 1-4 interactions: fudge = 0.5
Generated 3486 of the 3486 1-4 parameter combinations
Program: gmx grompp, version 2023.1
Source file: src/gromacs/gmxpreprocess/topio.cpp (line 577)
Syntax error - File entacapone1_GMX.itp, line 3
Last line read:
'[ atomtypes ]'
Invalid order for directive atomtypes
For more information and tips for troubleshooting, please check the GROMACS
website at http://www.gromacs.org/Documentation/Errors
please help me to solve this problem, and I will be very grateful to you
I am trying to do docking in MOE. I tried protonating 100 ligands in the same order, but the system said that the size of the vector was exceeded. Do you know how I can correct this? Or what is the maximum size of the matrix to protonate?
or what is the correct procedure to prepare the ligands in MOE? :(
I have been trying to dock a certain protein with nd ion i downloaded from rcsb but after i add it to pyrx and try to convert it to ligand i get the following error. I tried converting the sdf file to pdb using pymol, chimeraX, avogadro, open babel but even then when i open the file it gives me this error: ligand: :UNK0:Nd and ligand: :UNK0:Nd have the same coordinates. Could someone please help?
Update: I want to dock an unbound protein with the neodymium metal ion which i downloaded from rcsb in sdf format and later tried to convert it to pdb using the aforementioned softwares for autodock to accept it but i can't get it to be accepted by autodock as a proper ligand. Apparently I am unable to get any of the rare earth elements to be accepted properly as ligands.
I want to do docking validation. I downloaded the protein from PDB and deleted the chains and cofactors and saved the co crystal in .pdb format from discovery studio visualizer. Subsequently, performed docking of cocrystal ligand. Then I had drawn the co crystal ligand in chem draw and energy minimized the ligand and the docked. When I open the docked conformer of both in discovery studio, the conformers merge into each other and while calculating rmsd, it shows an error - "Element types not matching the reference ligand". Kindly suggest am I going with the right method. What is the alternative?
I am trying to create ligand topology and parameter files using SwissParam webserver. I followed all the steps to create the .mol2 file available in SwissParam page: https://www.swissparam.ch/SwissParam_mol2_file.html.
But this error keeps on coming:
Unfortunately, topology and parameters were not successfully generated for LIG.mol2. A failure report can be found below. Failure report: Possible problem with molecular topology in LIG.mol2. SwissParam will try to reconstruct the topology from coordinates only. Topology and parameters were NOT generated. Please check the validity of your molecule. - Are all hydrogens present in the mol2 file? - Is the mol2 file correct? Please, read "How to obtain a correct mol2 file?" in the www.swissparam.ch website.
For reference, I am providing my ligand.mol2 file and lig_fix.mol2 which I have created for performing protein-ligand simulation using Gromacs and CHarmm27 forcefield.
Please help me solve this query.
Thank you for consideration.
Hello, I've been attempting to simulate a beta cyclodextrin and drug inclusion complex, where this drug is one that I'm working on for a research project and can act as a ligand. The idea was to have the cyclodextrin act as a receptor to create an inclusion complex, but I haven't been able to achieve this. I have some experience with Autodock4 so I do know that protein-ligand interactions can be simulated with ease. However, I recall reading a post a few days ago that had me thinking if my efforts were for naught. Several commenters claimed the software wasn't viable for simulating these types of interactions. Could anyone please enlighten me on this?
I have recently faced a challenge purifying nuclear receptor proteins, specifically the Ligand Binding Domain. The wild-type protein expreses very well and I can purify it from frozen pellet. However, these two mutants that I am studying (M346V/T), I cannot get any protein from frozen bacteria cell pellet. So I need to use fresh bacteria cell pellet every time. Once purified the WT and mutant proteins are stable and I can freeze them. I am wondering why. Have you ever seen this? Do you have any clue of how these mutations can cause it?
Thank you very much for your help.
A Complete detail of all the interactions present between the ligand and DNA.
I have tried to contact the BIOVIA DiscoveryStudio support team, somehow my browser does not allow me to open their "contact form". I am trying to visualize and perform an analysis on a protein:smaller molecule complex. The smaller molecule happens to be a long peptide. Whatever I do with the PDB (change ATOM cards to HETATM, change residue names to PEP, UNK, LGD, introduce MODEL and ENDMDL cards) DiscoveryStudio indicates the input PDB file doesn't contain any ligand. Would any on ResearchGate have an idea of how to specify that a part of a coordinate file is the ligand, so that DiscoveryStudio 2021 recognises it as such and allows me to proceed? Thanks, Fred.
I have a protein. It's binding site are not known hence I used castp for the prediction. I set the grid box in autodock vina and performed the docking with a ligand. However, when I see the docking, the ligand was not bind to its pocket where I have set the grid. Looking forward for suggestions.
I am using AutoDock 4 for covalent docking. I wonder - is it possible to provide as input a pdbqt file with multiple ligands included, and later parse the dlg output accordingly? If so - what main modifications are required to the docking process, and is there a tutorial (or examples of the format of the batched pdbqt input and output files) available? Thanks!!
I've performed molecular docking using ClusPro. One of the chain from the ligand merged to a chain from the receptor when I wanted to study the protein-protein interaction using iCn3D. Thus, I unable to study the actual interaction of the protein and ligand. How to avoid ligand and receptor protein chain from merging into one chain after molecular docking? Or is there any other software that I can try to perform docking and study the interaction of the docked proteins?
I encountered an article that is about enhanced sampling method of protein - ligand system.
The paper is 'Ligand Gaussian Accelerated Molecular Dynamics (LiGaMD): Characterization of Ligand Binding Thermodynamics and Kinetics'. (J. Chem. Theory Comput. 2020, 16, 9, 5526–5547)
The following sentences appear in the paper.
"Next, one can add multiple ligand molecules in the solvent to facilitate ligand binding to proteins in MD simulations. "
"Multiple ligand molecules are added to directly increase ligand concentration in the solvent and enhance ligand binding in LiGaMD simulations. "
How to add multiple ligand molecules to the simulation?
I would appreciate it if you could let me know which tool has such a function.
Hello every one, I am using Charm-gui for molecular dynamics While i am uploading the protein complex in solution builder "Error parsing HETAT, expected chain ID at column 22, but got '': HETATM 1 C. Please help me to troubleshoot. Thank you
I am currently working on the simulation study of a complex whose ligand cannot be automatically parameterized. I have been using AMBER to do the parameterization, and now I have obtained the .lib for the ligand. I want to load the parameter to the complex to prepare the input file for simulation. After changing the residue and chain name of the ligand in the complex PDB, I did:
tleap -f oldff/leaprc.ff99SB
>complex = loadpdb deoxyCom.pdb
and it added missing heavy atoms that are not included in the parameter lib. (the whole message is as tleap.txt)
how should I deal with the problem and prepare the input file for MD?
After running this step to create ligand topology for molecular dynamic simulation protein-ligand complex:
python3 cgenff_charmm2gmx_py3_nx2.py ligand ligand_fix.mol2 ligand.str charmm36-jul2022.ff
It showed some tracebacks and import error:
ImportError: cannot import name 'gcd' from 'fractions' (/usr/lib/python3.10/fractions.py)
Does anybody know how to fix this problem in Ubuntu with python3.10 version?
#gromacs #topology #moleculardynamics
I tried to generate charmm36 topology and parameter files for copper ions on laccase enzyme but it presents an error that says "No residue in CHARMM forcefield". So I've tried CSML Search to parameterize ligand FF using PDB coordinates but the erros persists.
I have processed 100ns MD simulation studies with only protein and protein with ligand (with various analyses like- RMSD, RMSF, rGy, hbond etc) but the reviewer asks to calculate the solubility (water layer) and hydrophobicity change between unbound and ligand-bound protein. Does the reviewer mean to calculate the SASA or MM/PBSA with or without ligands?
i put the pdbqt files into autodock 1.5.7 to check the rmsd value. but one does not shows up and the other has a high value for model 1 even though its position more or less the same as model 2. Thank you in advance also i docked using vina if that helps.
I want to perform a MD simulation of a protein-ligand system after performing a molecular docking using the Autodock Vina plugin of UCSF Chimera.
When preparing the ligand for docking (using the "Minimize Structure" module of Chimera) I noticed that the bond order of two carbon atoms get messed up and both carbons end up becoming hypervalent (valency = 5).
This is causing problems further down the line when I try to parametrize the ligand using CGenFF or SwissParam for the MD simulation.
This is the 2D structure of the ligand before preparation (https://drive.google.com/file/d/1-_9RFXtP_uz2WQTaYb0t9myDJtgo1Pxd/view?usp=sharing).
This is the 2D structure of the ligand after preparation (https://drive.google.com/file/d/1Xf2xr1b_a-KXFEtNRsFaI-j--09TrikL/view?usp=sharing)
The ligand file is originally in SDF format which Chimera converts to MOL2 format during the preparation.
I am attaching the SDF and MOL2 files here as well. I hope it helps anyone who kindly looks into this issue.
I don't know what is causing this issue and I don't know how to fix it.
Any help/advice will be greatly appreciated.
Can anyone give a brief explanation about the relationship between ligand size (specifically, ligands smaller than 200 MW) and binding affinity in the in silico docking?
With the increasing of MW, can there be more false positives?
Really appreciate if you can give an idea about above matter or suggest a paper that deals with above issue...
I am working on a molecular dynamics simulation in protein-ligand system, using NAMD software, and I got the following error.
"FATAL ERROR: UNABLE TO FIND ANGLE PARAMETERS FOR HGA1 CG3C51 SG311 (ATOMS 1753 1752 1770)"
The atoms mentioned above belong to the ligand structure. The .str and topology files for the ligand were generated using Charmm-gui. Can someone help me to solve this failure? Thank you in advance.