Ligand - Science topic

Hi guys, I'm stuck on my research, can someone help me to explain how to dock the ligand with a cofactor NADPH using autodocktools ?

Is there a way to calculate the docking score of the zinc bound to this amyloid protein https://www.rcsb.org/structure/1ze9 without undergoing the docking procedure which is apparently not possible with MOE when the ligand is a single atom? I've heard that MetalDock can dock metal ions but the only thing I'm interested in is calculating the docking score of the zinc

I want to perform synthesis of reported compound can you suggest some techniques to find novel compound with better results

Hi

Can please tell me, To analyze the results of molecular docking and simulation of molecular dynamics (MD) of enzyme and ligand in Gromacs, what other analyzes can be done on them that can be discussed as a separate issue, except for usual analyzes such as RMSD, RMSF, Radius of Gyration, PCA, Gibbs free energy, GMMPBSA?

Thanks a lot

Dear connections I want to perform scaffold hopping of some molecule to get novelty on the reported compound can you suggest me the best software for the same. your support will be appreciated thank you

I'm docking an enzyme by using maestro, there is an metal locate at the docking active site, I have already tried a few methods but there are still show the metal is interact with ligands in glide result.

Hello, the image below is my cyclic voltammogram for a redox reaction with a metal and a ligand. Should I change certain parameters from during analysis? Or do you have any recommendations.

Thank you very much.

Sincerely,

Flynne D.

while trying to generate CGenFF topology for Ligand after extracting from docked file, i got error which i'm showing as a picture. What could be the possible reason and how will i rectify it for smooth running of MD simulation.

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

I'm designing a covalent inhibitor on an in silico study. Should I use the "pre-reaction" non-covalent ligand-protein complex or covalently bonded one on the Molecular Dynamic simulation input?

I think it's necessary to know how long the ligand stays in the binding site before the colavent-bond-forming reaction occurs. While it is probably a femtoseconds-process that does not need such nanoseconds stability. So it is more beneficial to do MD on the covalent-bonded complex to evaluate how strong its resident time is (and the inhibitory potential). The TS-DFT calculation suggests that the covalent bond may be reversible. However, I am not sure that MD can represent bond-breaking reactions. I still haven't gotten any concrete data on how several studies did it. Please give me your opinion. Thanks

Hi

I am practicing molecular docking using PyRx software. In articles, mostly Gaussian software is used to publish the molecular docking of any compound. Can be publish any molecular docking using PyRx (studying docking) and Discovery studio (studying ligand protein interaction, etc). Infect I am a beginner, and it is difficult to use Gaussian.

I have synthesized various Schiff base ligands, two of them are given here, upon coordination with metal such as Dy (NO3)3.5H20 and CoCl2.6H20, the ligands tend to break, what could be the possible reason and how to avoid the breaking of ligand. The solvent combination used for the reaction is C2H5OH+CH3CN in the presence of Triethylamine. Good suggestions and solution are welcome.

Thank you very much in advance.

I want to increase the number of conformations which is by default 10. I want to get 100 conformations of a single ligand. Is it possible using autodock vina or any other software?

Hello everyone,

While performing MD simulations of protein - ligand complex, at the adding ions stage I am facing an error :

Fatal error:

Syntax error - File UNK_fix.itp, line 7

Last line read:

'[ atomtypes ] '

Invalid order for directive atomtypes

Well, since I've used Swissparam to write the topology file of the ligand (UNK_fix.gro) which usually uses CHARMM all atom forcefield and the protein topology I've written with the charmm36-2019.ff. Can this be a reason that I'm facing the above error?

I've also referred to other options like #include statements which I suppose are correct and the editing in topology is all done right. For reference:

; Include Position restraint file

#ifdef POSRES

#include "posre.itp"

#endif

; Include ligand topology

#include "UNK_fix.itp"

; Include water topology

#include "./charmm36-mar2019.ff/tip3p.itp"

#ifdef POSRES_WATER

; Position restraint for each water oxygen

[ position_restraints ]

; i funct fcx fcy fcz

1 1 1000 1000 1000

#endif

; Include topology for ions

#include "./charmm36-mar2019.ff/ions.itp"

[ system ]

; Name

Protein in water

[ molecules ]

; Compound #mols

Protein 1

UNK 1

SOL 24553

So, please guide me through any other suggestions which may correct this error.

Thank you in advance!

I merged heme and a ligand by manually editing gro and top instead of “-merge”, after which MD was performed. This result was unexpected for me because heme is not covalent binding to the protein, and it and the ligand are separated from the protein in less than 10ns of MD, but the ligand can only be injected once, so how do I make sure that the protein and heme are integrated as a whole, and MD of the ligand with the conjugated protein I constructed?

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.

Hello everyone,

I am working on DNA with two covalently bound modified cholesterol chains. I am unable to make the pdb2gmx file. I have generated the itp and prm file using CGENFF python script. But, I am unable to proceed further as the rtp file for the modified cholesterol and the parameters required are not present. Can anybody tell me the procedure for generating the pdb2gmx file for DNA with the covalently bound ligand.

Thank you in advance

hello,

can anyone help me with finding the solvent for iron ethoxide except ethanol and for iron isopropoxide except isopropanol.

I will be very thankful.

This is occurring after uploading the pdb file of docked protein ligand complex from auto dock.

I was looking for an antibody that can block the ligand binding domain of mouse EGFR. Can I use Cetuximab or is it exclusively human-specific?

I have been trying to run Autodock Vina for my undergraduate thesis for many months have have been getting the following error. Does anyone have any ideas? I have attached an image but if that cannot be opened here is there error message through Cygwin64:

Reading input...

Parse error on line 1 in file "2jgd_DOCK.pdbqt": Unknown or inappropriate tag

mv: cannot stat 'ligand*.pdbqt': No such file or directory.

Please help!

I am running docking by using Autodock 4.2 software. However, I am not able to run autodock at the final stage and this type of command error appears in the terminal,

Unknown ligand atom type "atotypin"; add parameters for it to the parameter library first!

Autodock 4.2 runs without errors for similar ligands but this error is seen with ligands having Br and Cl groups.

I edited the autodock parameters tool, But still I faced current problem

I performed virtual screening of some molecules in Auto Dock Vina and GOLD and obtained different results for the best ligand. I'm not sure if I did something wrong, or the docking program is not the most appropriate for my protein and ligands, or the difference is due to the different interaction analysis algorithm.

The protein does not have a co-crystallized ligand, so I did not validate the program by redocking. I'm following the active site predicted by COACH-D. I don't know if this is relevant when comparing results from two different programs.

Dear experts,

I am trying to perform a production run of several proteins in a water environment according to several tutorials. After the production, one of the analysis I am interested in is the evaluation of a radial distribution function around each bead of the chain.

I am trying with the module gmx rdf but I am havint some trouble in specifying that the calculation should be done for a specific segment and not the center of mass of the entire chain. Do you have any suggestion?

Thanks in advance.

I tried to coat a ligand layer on the surface of the TiO2 thin film using an oil bath reflux system at 40 degrees Celsius for 24 hours. Previously, I observed the NH2 peak at 1250 cm-1 in FTIR analysis. Currently, I'm unable to determine the repeatability of past data. I'm using DMF solvent. I also tried different parameters like temperature, time, concentration, and solvent.

Can anyone explain what is happening here? If my TiO2 surface is changed, or are there any mistakes from my side? I would like to get advice from people with similar experiences or related experts.

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?

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

I am doing an M-L complex (metal is Fe and ligand is tetra co-ordinated) optimization using 12 processors and SCF=QC keyword. How many days it will required to complete the calcuations. Its already been 10 days and I am not sure whether the calcultaions is running correctly or not?

So if I want to know what the structures are for different regions in the 2D projection plot of PCA analysis, how would I proceed? Any idea?

i am trying to grow TTV on 293T, Jurkat, and A549 cell lines for a prolonged period. As the replication mechanism of this virus is not fully understood, I want to check what receptors on these cell lines are facilitating the attachment of the virus.

I synthesis new ligand, that ligand react with divalent metals it forms metal complex. l used maestro 9.0 for docking the protein with ligand but the problem was maestro 9.0 (not only that all the docking software) not accepted the coordination bond between the metal and ligand in the .mol or .sdf format.so how to dock metal complex with protein.

I have run a MD simulation for a protein-ligand system using AMBER. There are multiple binding poses for the ligand during the simulation. I want to find out some representative binding poses of the ligand. How can I achieve this? I have tried the dbscan clustering by calculating the pair RMSD of every snapshots and I think it is not a good way.

If a compound has a lot of oxygen moities in ligand, so the docking score will be increase? If it will increase then what is the reason behind it?

Hello RG Community I hope you're well:).

For the above topic I only need to optimize two-dihedral angles, can I therefore

only select Scan and Opt Torsion tabs and ignore the others i.e. Opt Charge etc.?

(My goal is to simulate a protein-ligand Complex via Gromacs and my ligand exhibited

only two penalized dihedral angles needing optimization before proceeding any further.)

Thanks if you know:) Joel 

I am running a protein ligand complex simulation using Gromacs 2021 on a Windows Subsystem for Linux. My laptop has Nvidia GeForce RTX 3050 GPU. When i run the simulation of Lysozyme tutorial (as given in GROMACS tutorial) for 100ns, the expected finish time is showing approximately 1 week. I looked at the topology file to get an understanding of system size and found that my total system size is approximately 47500 including Solvent, ions, protein and ligand.

1) The "dt" defined in the mdp file is 2 fs and the number of steps (nsteps) is 50000000. I wanted to know if there is a way to speed up the process or is this the natural computation time that RTX 3050 provides? I went through other queries about the same issue and also I have worked with RTX 3080 Ti which completes a 100 ns simulation in approximately 30 - 40 min. So I assume that since 3050 also belongs to a similar class/family as that of 3080 Ti, it should atleast provide a better simulation timing (say 100 ns in 1-2 hours). I might be wrong about the technical aspect of GPU computation. Any help in this matter will be much appreciated.

2) Also, I wanted to know, since I am running these simulation in Windows Subsystem for Linux (WSL2), does that affect the computation speed of the GPU when MD Simulations are run using GROMACS?

I would appreciate if someone can help me out in this regard.

Thanks

Satyam

I am considering running an MD simulation of a protein with varying ligand concentrations. I think replica exchange molecular dynamics should be able to do that, but I have no idea how that is done.

Is it possible to get a tutorial or possibly other methods for running such a simulation?

Dear all,

I performed a simulation of a membrane-transporter and ligand for 50ns.

During the simulation, and as I expected, the ligand comes out of the transporter protein and does not come back. However, after the removal of PBC, the ligand jumps to the other side of the membrane which is not possible at all. With careful visualizing of the system using VMD, I am convinced it is a PBC problem in the mol stage. I put the commands I used for PBC removal and I also attached the movies from the clustering and mol stages.

I would appreciate any help.

gmx trjconv -s step7_production.tpr -n index.ndx -pbc whole -f small.xtc -o whole.xtc

gmx trjconv -s step7_production.tpr -n index.ndx -pbc nojump -f whole.xtc -o nojump.xtc

gmx trjconv -s step7_production.tpr -n index.ndx -pbc cluster -f nojump.xtc -o cluster.xtc

gmx trjconv -s step7_production.tpr -n index.ndx -pbc mol -f cluster.pdb -o mol.pdb -ur compact

Dear all,

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:

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?

Hello,

I have recently switched from doing ligand into protein for ITC because my ligand is in DMSO and has low solubility at 10% DMSO; therefore, now I am doing protein into ligand -- the heat transfers are much better and seem to correlate to the protein concentration loaded in the syringe which is good to see.

However, at the end of my titration regardless of the concentration of ligand or protein added there is an increase in heat transfers. I am also seeing this in my protein injections into buffer alone.

Any thoughts on why this might be happening?

Hi!

Does anyone have ideas to separate Fe(II) complexes from Fe(III) complexes?

Context about the complexes:

1) Coordination of the ligand causes some type of Fe(III) to Fe(II) reduction (Always starting with Fe(III) sources)

2) They are neutral complexes that are coordinated by a macrocycle with three carboxylic acid groups and a fourth group that may or may not be coordinating

3) The only difference between the two complexes is one carboxylic acid is assumed to be uncoordinated in one

4) Most contain at least one CF3 group but the reduction behavior is seen in all of them

5) Less hydrophobic complexes can be separated reverse phase chromatography but the more hydrophobic they get the harder it is to separate

6) Complexes don't seem very stable on silica or alumina oxide gels

Edit to add that the Fe(II) complex is air-stable and I'm actually trying to isolate pure Fe(III)

Hello,

I am having an ITC issue because I cant increase my ligand concentration due to solubility issues.

I know there is past literature on reverse titrations being acceptable. I am more asking about what concentrations I should try for the reverse titration.

I have used fluorescence polarization as a competition based assay showing a Ki of around 10μM for the ligand titrated into protein. Can this help me in determining concentration of protein/ligand for a reverse titration?

I have tried titrating ligand into protein at the maximal concentration of ligand and there is a slight but significant heat change; therfore, Nanoanalyze has suggested I increase ligand concentration -- that is why I amm trying to do a reverse titration now. Thanks for your help.

i am doing oniom calculation QM/MM for CYP450 and a drug as ligand. here i put my input file and the log file. i have been building this system for 3 weeks. this time i can't find out where the error is. i still think it is the problem in my mm parameters. also, the former error is bond and angle are not defined (in my ligand and the heme molecule). so i deleted all the connections of them and this error was solved. is this operation okay?

Hello, the image below is my cyclic voltammogram for a redox reaction with a metal and a ligand. Can you help me explain why I see two reductions and two oxidation cycles, respectively? What can it imply?

Recently I've done the synthesis of a water-soluble ruthenium complex with 1H-imidazole. I could separate the desired complex from other complexes formed during the synthesis by chromatography(silica gel), but I haven't been successful in the separation of the complex and the 1H-imidazole ligand. I already tried chromatography and washing with some organic solvents (the problem is that all that imidazole is soluble my complex is soluble as well). Does someone have any suggestions for this problem?

I am currently working to dock a ligand at a receptor and working on autodock 1.5.6 and the map files are not being generated , as the autogrid run is unsuccessful, I have previously done this but this time I am unable troubleshoot as to why .gpf file is not being able to generate or being able to be read by autodock?

I have run a docking of Actinonin on 2OS3 and got an optimized coordinates for the grid box to result in rmsd less than 2. However, when I tried to visualized it using Biovia discovery studio, the ligand (Actinonin) doesn't appear. I have docked it several times, but still can't show the ligand in Biovia.

oyea, when I checked it by using chimeraX, the ligand can appear in the complex with the protein. but still, in the Biovia discovery studio resulted nothing.

Any suggestion, please!

While performing STD screening I noticed that I have signals in my difference spectras, that are constant accross all samples, also if there is no ligand and only protein.

The protein was purified via size exclusion and is in deuterated PBS.

I am currently looking for any tools to analyze the probable docking sites intead of going for blind docking. Is there any bio-informatics tools or webserver that can help me further analyze the pockets present in my protein of interest and export the co-ordinates.

I am working on nanobody based purification system and in order to reuse it, I have to separate the nanobody from its ligand.

Hello,

I am doing ITC and getting repeatable curves that look very promising. After reading some articles, it seems the biggest challenge to avoid is buffer mismatch. Is there a way to rule out that my curve is indeed ligand to macromolecule binding rather than buffer mismatch (i.e. shape/values of curve, shape/values of trace, thermodynamic values)?

I am very careful when preparing my samples but because my ligand is a small molecule I can't dialyze. I am pretty certain my buffers are well matched but I just want to be certain.

Any help would be appreciated.

Hello,

I am using Autodock4 and AGFR to perform in silico docking experiments with a small molecule, triptolide, and a human protein, XPB (ERCC3). I am running on windows 11. I only experience this issue when performing docking with flexible residues.

I prepared the ligand file using the Autodock Tools interface. The prepared ligand file is below:

REMARK 2 active torsions:

REMARK status: ('A' for Active; 'I' for Inactive)

REMARK 1 A between atoms: C_4 and C_2

REMARK 2 A between atoms: O_23 and C_17

ROOT

ATOM 1 C UNL d 1 29.320 -35.802 -65.656 0.00 0.00 0.010 C

ATOM 2 C UNL d 1 30.655 -36.509 -65.505 0.00 0.00 0.020 C

ATOM 3 C UNL d 1 31.481 -36.415 -66.786 0.00 0.00 0.010 C

ENDROOT

BRANCH 2 4

ATOM 4 C UNL d 1 31.414 -35.962 -64.276 0.00 0.00 0.129 A

ATOM 5 C UNL d 1 32.206 -34.626 -64.232 0.00 0.00 0.186 C

ATOM 6 C UNL d 1 33.144 -34.610 -63.021 0.00 0.00 0.156 A

ATOM 7 O UNL d 1 33.172 -33.137 -63.096 0.00 0.00 -0.359 OA

ATOM 8 C UNL d 1 34.431 -33.885 -63.005 0.00 0.00 0.157 A

ATOM 9 C UNL d 1 32.606 -35.189 -61.637 0.00 0.00 0.138 A

ATOM 10 C UNL d 1 35.436 -34.297 -61.794 0.00 0.00 0.043 C

ATOM 11 C UNL d 1 34.996 -35.365 -60.947 0.00 0.00 0.030 C

ATOM 12 C UNL d 1 33.528 -35.393 -60.451 0.00 0.00 0.009 C

ATOM 13 C UNL d 1 36.026 -35.404 -59.931 0.00 0.00 -0.019 C

ATOM 14 C UNL d 1 33.535 -33.891 -60.010 0.00 0.00 0.015 C

ATOM 15 C UNL d 1 33.129 -35.753 -59.204 0.00 0.00 0.015 C

ATOM 16 C UNL d 1 34.291 -35.969 -58.106 0.00 0.00 0.043 C

ATOM 17 C UNL d 1 35.635 -35.641 -58.522 0.00 0.00 0.039 C

ATOM 18 C UNL d 1 36.885 -35.753 -57.845 0.00 0.00 0.336 C

ATOM 19 O UNL d 1 37.997 -35.493 -58.737 0.00 0.00 -0.457 OA

ATOM 20 O UNL d 1 37.016 -36.031 -56.771 0.00 0.00 -0.245 OA

ATOM 21 C UNL d 1 37.485 -35.611 -60.106 0.00 0.00 0.264 C

ATOM 22 C UNL d 1 31.529 -36.108 -61.742 0.00 0.00 0.186 A

ATOM 23 O UNL d 1 31.351 -34.850 -61.074 0.00 0.00 -0.358 OA

ATOM 24 C UNL d 1 31.536 -36.827 -63.142 0.00 0.00 0.185 A

ATOM 25 O UNL d 1 32.525 -36.859 -64.163 0.00 0.00 -0.359 OA

BRANCH 5 26

ATOM 26 O UNL d 1 31.029 -33.875 -64.291 0.00 0.00 -0.386 OA

ATOM 27 H UNL d 1 31.242 -32.949 -64.278 0.00 0.00 0.210 HD

ENDBRANCH 5 26

ENDBRANCH 2 4

TORSDOF 2

I entered the following command into the command line:

C:\Users\gorri\OneDrive\Desktop\Fan Lab\Docking\Autodock4\HsXPB\HsXPB_7NVVSite2FlexReceptors&EnlargeGridtoBoxFlexResidues>autodock4 -p dockywocky.dpf -l results.dlg

Then I get the following error message:

autodock4: FATAL ERROR: autodock4: ERROR: All ATOM and HETATM records must be given before any nested BRANCHes; see line 39 in PDBQT file "TLI_model.pdbqt".

So, then I changed the ligand file to the following to force it to work:

ATOM 1 C UNL d 1 29.320 -35.802 -65.656 0.00 0.00 0.010 C

ATOM 2 C UNL d 1 30.655 -36.509 -65.505 0.00 0.00 0.020 C

ATOM 3 C UNL d 1 31.481 -36.415 -66.786 0.00 0.00 0.010 C

ATOM 4 C UNL d 1 31.414 -35.962 -64.276 0.00 0.00 0.129 A

ATOM 5 C UNL d 1 32.206 -34.626 -64.232 0.00 0.00 0.186 C

ATOM 6 C UNL d 1 33.144 -34.610 -63.021 0.00 0.00 0.156 A

ATOM 7 O UNL d 1 33.172 -33.137 -63.096 0.00 0.00 -0.359 OA

ATOM 8 C UNL d 1 34.431 -33.885 -63.005 0.00 0.00 0.157 A

ATOM 9 C UNL d 1 32.606 -35.189 -61.637 0.00 0.00 0.138 A

ATOM 10 C UNL d 1 35.436 -34.297 -61.794 0.00 0.00 0.043 C

ATOM 11 C UNL d 1 34.996 -35.365 -60.947 0.00 0.00 0.030 C

ATOM 12 C UNL d 1 33.528 -35.393 -60.451 0.00 0.00 0.009 C

ATOM 13 C UNL d 1 36.026 -35.404 -59.931 0.00 0.00 -0.019 C

ATOM 14 C UNL d 1 33.535 -33.891 -60.010 0.00 0.00 0.015 C

ATOM 15 C UNL d 1 33.129 -35.753 -59.204 0.00 0.00 0.015 C

ATOM 16 C UNL d 1 34.291 -35.969 -58.106 0.00 0.00 0.043 C

ATOM 17 C UNL d 1 35.635 -35.641 -58.522 0.00 0.00 0.039 C

ATOM 18 C UNL d 1 36.885 -35.753 -57.845 0.00 0.00 0.336 C

ATOM 19 O UNL d 1 37.997 -35.493 -58.737 0.00 0.00 -0.457 OA

ATOM 20 O UNL d 1 37.016 -36.031 -56.771 0.00 0.00 -0.245 OA

ATOM 21 C UNL d 1 37.485 -35.611 -60.106 0.00 0.00 0.264 C

ATOM 22 C UNL d 1 31.529 -36.108 -61.742 0.00 0.00 0.186 A

ATOM 23 O UNL d 1 31.351 -34.850 -61.074 0.00 0.00 -0.358 OA

ATOM 24 C UNL d 1 31.536 -36.827 -63.142 0.00 0.00 0.185 A

ATOM 25 O UNL d 1 32.525 -36.859 -64.163 0.00 0.00 -0.359 OA

ATOM 26 O UNL d 1 31.029 -33.875 -64.291 0.00 0.00 -0.386 OA

ATOM 27 H UNL d 1 31.242 -32.949 -64.278 0.00 0.00 0.210 HD

TORSDOF 2

I then get the following error message:

autodock4: FATAL ERROR: autodock4: ERROR: All ATOM and HETATM records must be given before any nested BRANCHes; see line 1 in PDBQT file "TLI_model.pdbqt".

Any help is greatly appreciated. Thank you.

ERROR 1 [file topol.top, line 55398]:

atom O5 (Res HIS-1) has mass 0 (state A) / 0 (state B)

ERROR 2 [file topol.top, line 55398]:

atom O6 (Res HIS-1) has mass 0 (state A) / 0 (state B)

ERROR 3 [file topol.top, line 55398]:

atom H31 (Res HIS-1) has mass 0 (state A) / 0 (state B)

ERROR 4 [file topol.top, line 55398]:

atom H32 (Res HIS-1) has mass 0 (state A) / 0 (state B)

ERROR 5 [file topol.top, line 55398]:

atom H33 (Res HIS-1) has mass 0 (state A) / 0 (state B)

ERROR 6 [file topol.top, line 55398]:

atom H34 (Res HIS-1) has mass 0 (state A) / 0 (state B)

I'm following a protocol to bind fluorescent ligand to receptors expressed on cells in a microplate. The protocol includes fixing cells with 4% PFA for 20 mins. This prevents cell loss during washing. But this ligand will only bind if the receptors are coupled to intracellular G proteins. Does fixing the cells kill these intracellular proteins?

Good day,

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.

Hello,

I want to perform 100ns GROMACS simulation using CHARM27 force field on a protein-ligand complex where my protein is CYP51 (PDB ID: 5V5Z) which contains a heme group covalantly bonded to the ligand.

All the files are placed in a specific folder in C drive. (it includes the protein and ligand pdbqt files, autodock4.exe, autogrid.exe and dat files from mgl tools 1.5.7). After repeatedly running from several times till date, I am forced to seek help to further carry out my studies. Please help in any way possible. Thank you.

I selected Md_0_10.gro file and then md_0_10.xtc file then I got something weird like this in the video in vmd, can someone pls suggest what's wrong in this step?

Is it mandatory that the grid box has to be localized specifically at the same exact site where the reported inhibitor binds to the receptor? Is there any relevance for carrying out blind docking for a new drug (ligand) against a protein when already the site of inhibitor and protein binding is known from experimental XRD structure.

While trying to import Autodock session (AutoDockTools 1.5.7) I am receiving an error (attached below). All files work during simulations, yet it is impossible to open saved session file.

mol.2 file (attached below) does not seem to be corrupted (since it works while starting the simulation from the very beginning)

Part of the error message:

The file ligand_optimized doesn't contain any mol2 records

The file ligand_optimized doesn't have Atomrecords, molecules can't be built

Hi, I ran COFACTOR and COACH servers many times for my enzymes to predict their ligand receptors and function prediction, and the website answered would send the result to my email, but I didn't receive any result for more than one week I don't know where is the problem I checked my email its work and receive other emails. Can anyone suggest what to do, the server assumed to send the result via email after 10 hours but no answer till now. Thanks

Dear RG Community,

I am validating my docking protocol by re-docking the co-crystalized ligand into a defined pocket.

After docking, I am getting a pose which is flipped around its axis in 180 degree than that of the co-crystalized one.

Surprisingly, RMSD was also very less (below 1.2 Angstrom) between docked and the co-crystalized poses.

Could you please suggest possible reasons and the solution on it.

Thank you.

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?

Thank you

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

And I was using imidacloprid for molecular docking. When setting the ligand, the charge of imidacloprid was always calculated to be 0, and the docking reality was wrong.

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?

Thank you

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?

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.

Thanks

Greetings everyone,

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.

Hi,

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.

Hello,

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.

Thank you.

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.

Thank you.