EP 10 | Protein-Ligand MD Simulation in Gromacs-A to Z | all reusable commands and files provided

Hi,
I am Dr. Dweipayan Goswami,
Welcome to my KZbin channel "Learn at ease"
In this video I have provided the full tutorial with universal codes that can be used to perform MD simulation with Gromacs with any Protein-Ligand complex by following the exact same procedure represented in this video
Tutorial, Codes and Files used in this video will be found at Github :
github.com/Dwe...
The files of protein ligand complex is the docked complex which I had prepared in my video :
EP 1 | MOLECULAR DOCKING in UCSF CHIMERA by VINA Plugin from Scratch in Linux
• EP 1 | MOLECULAR DOCKI...
Other important videos available in the Playlist :
• Bioinformatics-Unplugged

[@karukuvelrajaraja6101]

Thank you so much even very know persons can't teach me this past 2 months lot of errors and mistakes finally I saw your video truly I can't got any errors successfully I done this thank you very much sir

[@carolinemaina4062]

You are a lifesaver. Everything works perfectly. Thank you so much for such a detailed presentation

[@945corleone]

Dear teacher, as always, it is a very detailed, useful video. I pray for you. I'm glad you are.

[@jeremiascorradi7865]

Thank you so much!!! your explanation was so clear and everything worked perfectly well.

[@niveditasingh5837]

Thank you so much sir. This video has been fundamental for me to learn MD simulation. Please upload video to calculate cross correlation matrix also. It is imperative for may work

[@khadijahtabassum7544]

Very helpful tutorial. Can u make a video on protein-protein MD simulations or can guide which server or method will be best for macromolecule interactions?

[@hritushreemog9333]

Hi, I wanted to get the parameter files but in swissparam it is saying file too big, Can you suggest some other servers from where I can download the parameter files

[@lemessaetana2011]

Very helpful demonstration. Thank you, Sir!

[@knowledgeseeker9757]

Tamaro khub khub aabhar 🙏

[@amazingrelaxingnature9761]

Hi Dr Thank you very much for all. i like all your videos. please make a video for MD simulation for nano drug and protein using gromacs

[@ofosuhemaajoyce9478]

Please concerning the editing we did at the MD.mdp Please is my calculation right Nsteps = 25000000 ; 2 * 25000000 = 50000 ps (50ns) Please is my calculation right

[@rahulvishvkarma5852]

Can you do 2 simulation for 2 different ligands with one protein structure. You'll be compensate for the same.

[@kankipatitejashyam2116]

Hello there, can you please tell me your system (PC/LAPTOP) specifications Thank you

[@curiousresearcher308]

so for nsteps at the end to run for 2ns can we replace 2*50000 with 4*50000?

[@hlatywayotinotenda3895]

from the tutorial, i am failing to understand how the protein-ligand interaction in Pose1 is maintained. Does it differ, lets say i have used pose3 or i have downloaded the ligand in sdf format and just converted it to mol2 format using open babel. May you please help me.

[@cake975]

Thank you so much for all the bioinformatics series as it is really helpful. Can I follow this tutorial for GPCR protein?

[@bassantmoustapha8145]

Thank you very much for your patience

[@DweipayanG]

Thank you

[@JellaMaruti]

Thank you so much for the super awesome tutorial. A quick question, do we have to run the equilibration run for NVT and NPT for exactl same time as that of md run (for eg 25 ns for all, NVT, NPT and md run)? Please let me know, thanks a lot again for all the hard work.

[@tanerduysak9270]

Thank you very much for this tutorials I have a question about the last part the movie section when I do my simulation some part of the protein seems to be out of the box and that parts looks like stretching out of the image. What do you think can make this issue. I mean first 200 frames are fine but after that that stretching start.

[@monahussain1938]

sir am always trying to create ligand topologies from swissparam but there is always an error although i follow all the steps

[@KenKaneki-ew2rm]

I want to extend the simulation from 100ns to 200ns. I used the extend command earlier but it does 200 from zero. I want to run it with continuation. Like the simulation should start from 100 ns to 200ns.

[@uttkarshverma9404]

sir the energy minimization command is not working( gmx mdrun -v -deffnm EM)

[@yenumalavamshidharreddy7361]

Did u find any solution to this...same happened to me

[@manishashah466]

either you can use -nt command or else make your protein once again as directed in the video It will solve your error

[@NAMELOVESTATUS]

can we perform md simulation online server, we have not graphics card

[@varshinikore3011]

2619 atoms are not part of any of the T-coupling groups I am getting same error every time plzzz suggest what to do

[@hamzaallal1867]

Thank you very much for your time and effort.👋👋 In the step of preparing the topology of the Ligand, in particular during the generation of the .str file (stream" file). I tried with a complex based on Iron II (organo-mitalic compound) but an error that blocks me, because element (iron) not supported. Please, Could you suggest me another method or another WEB server.

[@lotfibourougaa6209]

Dr.. I can not get the files from Swissparam, it seems that there are errors.. despite the extracted file is correct. could you help us? THANK YOU

[@DweipayanG]

I have no clue why swissparam is giving error I have noted that if the ligand molecule is too large in size then error occurs …. If thats not the case then try constructing molecule using smiles in chimera …. Tools > structure editing > build structure ………. Paste smiles and save 3d conformer in mol3. Use this molecule as starting point in docking …. After successful docking take it further for MD

[@Snehakaashid]

I got an error sir my cordinate file (box_sol.gro 23286) and topology file number( 21270 ) Did not match. Kindly help me . I follow your vedio since episode 8 till now it work smoothly but now this error arises

[@concept1994]

Wonderful

[@Arya_stark_95]

Hi Sorry, but there is a mistake at the beginning of the tutorial with the structure of the ligand. The molecular formula of Risperidone is C23H27FN4O2, 57 atoms not 58. I believe there is a plus hidrogen bonded to a oxigen.

[@DweipayanG]

Ok no problem..

[@drbipinraj]

When I am opening confo.gro in UCSF Chimera my ligand is not bound to the protein,instead it is far away from the protein. Why it is happening kindly guide me.

[@DweipayanG]

You might be dong some error in mol2 file in earlier step.

[@ES-yd1ze]

I faced this problem previously is that NORMAL ??

[@phuochuynh1777]

I have a note "Update groups can not be used for this system because atoms that are (in)directly constrained together are interdispersed with other atoms". How can i fix it sir. Thank you

[@santiagobeltran2088]

One question, after receiving the message of the existence of an incomplete ring, instead of choosing to complete the initial structure, you decided how to rewrite the pdb file even though there are missing residues in the protein. My question is, shouldn't it be advisable to have a complete structure for the dynamic execution? what is the difference between both scenarios?

[@muayadrdaiaan]

At the beginning, thank you very much for the wonderful information that you provided in all the KZbin series, regarding video No. 10, which included the MD process between Risperidone and protein, which was completed successfully, and I did all the steps that you explained on KZbin and also succeeded in reaching the same results as you (but I had to To wait seven hours in the MD.mdp step and the number of steps is 2ns). The problem I encountered is that I have new organic compounds that were not previously prepared, and I wanted to perform the same previous steps, but when I reach the swiss-param step, LIG ​​does not turn into topology. Can you repeat all the steps on new compounds that you draw in chemdraw, not from pubchem?

[@DweipayanG]

You can copy the smiles of your new compound in to UCSF chimera Tools>build structure , and then add hydrogens and then save its mol2 file. This prepared file should work well.

[@muayadrdaiaan]

I work this step but also failed. I want from you if you can made youtube explain all the steps from the beginning to this step,

[@muayadrdaiaan]

If you want from me send you a picture of my new organic compound, please send me your E-mail

[@muayadrdaiaan]

Regarding repeating the steps, my intention was to re-interfere my new compound(chemdraw) with the protein as in the video (EP 1 | MOLECULAR DOCKING in UCSF CHIMERA by VINA Plugin from Scratch in Linux), formation (pose 1) or (pose2), then take this (pose1) and work MD

[@samarshekh6385]

@@muayadrdaiaan did you resolve it?

[@ipinlojunureni8780]

Hi Dr. Thank you for the wonderful lecture When converting to a topology file, I am getting an error that Residue 'BRL' is not found in residue topology databases. How can I solve this issue sir?

[@yatin_57]

Good Evening Sir, Can I follow the same procedure for protein-protein MD simulation?

[@DweipayanG]

No you cannot follow this procedure for protein protein md

[@yatin_57]

@@DweipayanG Sir, I Literally learnt a lot from this series can u plz record a session for protein-protein MD it would be better for all of us to get an idea of PP-MDS..... Thank you:)

[@yatin_57]

Please Sir, :)

[@mahmoudelbeh3001]

you are amazing man thank you

[@mvkishore8954]

Hi, how do we have to choose ions (equilibration) for our system with the water box? Any theory or reference there?

[@anuamirtha477]

I am not able to generate the topology file there is again and again fatal error in residue gln as the atom Ca should be fixed

[@mandiraperera7396]

Hi, can u tell me how solve, when adding ions step, error 1( file lig.itp, line 20): atomtype NPYD not found... im in a trouble in my research. This cant be solve to me😢

[@saikatroy7923]

Sir will u plz hlp grompp comand does not work , it shows Fatal error: There is 1 error in input file(s)

[@rezafazl9024]

HI sir, If I runnig a complex simulation, Can I go to my other work with the system at the same time?

[@titonig4148]

Thank you very much for the tutorial. I've one answere: can I use the same parameters to perform protein-protein interactions? should i treat the second protein as ligand? Thank you so much!

[@titonig4148]

I've alrady performed the protein-protein docking using lzerd. Should I use the constrains file that I've used to perform the docking?

[@khadijahtabassum7544]

Have you done protein-protein MD Simulations?

[@pelinsuekmekci9072]

I have dimer protein and ligand how should looks like my topology file?

[@user-cg9fh2ik8g]

what if we want to change the ph of solvent?

[@abhishekdas6874]

Wil it be the same for AMBER forcefield

[@abhishekdas6874]

Best

[@wenkaiPan-fw8fh]

Dear teacher，every time when I run the gmx mdrun -v -deffnm EM, the terminal will show me segmentation fault (core dumped). I really don’t understand how to solve it, can you give me some advice? Thank you so much!

[@yenumalavamshidharreddy7361]

Did you any solution...same problem to me also

[@gabrielluisdarioloayzapret2941]

Muy buen video

[@alpbay100]

Dear Mr. Can Goswami or anyone else familiar with this help me with what changes I should make to NPT and NVT for the 100ns and 200ns simulations?

[@sivaramansharadat3430]

Can I run gromacs md simulations in windows

[@nikhilvenu]

yes, i am using windows subsystem for linux

[@arjunpahi]

in github, still correction in NVT.mdp not done....

[@DweipayanG]

Thanks for info i will update asap

[@youssrafatima3671]

Hello please the gmx genion -s .... boxsol ion .itp does not work with me i dont know but but alwys when i repeat the procedure it appears that there is no ion tpr file so how can i create it

[@binarysecrets9055]

Facing the same problem. Please help sir

[@kunchat1989]

Thank you very much. Is it mandatory to dock first ?

[@DweipayanG]

Nope

[@saraashraf5874]

Is simulation on gromacs take 5 days to complete one simulation process??

[@DweipayanG]

Yes it can … it all depends on ur computer power

[@curiousresearcher308]

5 days??!! you mean the steps right? or one step took 5 days? sorry I don't know actually I am just learning. or 5 days for all the steps?

[@DweipayanG]

Md simulation run can take long time if 1. Length of md simulation run is long i.e. 200 ns or so or 2. If gpu support is missing in computer

[@saraashraf5874]

@DweipayanG I have dell laptop core I 7 Ssd 256 gb My system got hang or stuck whenever I run md command Is their any way to tackle this problem?

[@DweipayanG]

No clue ! U use linux or windows ? It depends on how powerful your gpu is

[@rahulnaga5010]

Sir please make a video on gmx_MMPBSA.

[@phuochuynh1777]

Hello Dr, I have some questions. What is the function of NVT and NPT.mdp in MD? And the time-step in NVT and NPT must be the same as time similation? (Example: i see almost NVT and NPT have time-step is 50.000 step = 100ps when md.mdp has the time-step is 100ns)? Can you explain in details? Thank you so much

[@DweipayanG]

First the small MD runs are done with NVT and NPT which are called “equilibration” runs.. output of this is then used for long actual MD production run which is by the use of MD.mdp file which is modified NPT

[@phuochuynh1777]

@@DweipayanG So, the quilibration in 100ps that is enough for run MD, sir? If we increase the time of equilibration, is that mean increase the quality when we run the molecular dynamics?

[@DweipayanG]

Yes ...

[@kakadiyatulshi5286]

Hello what if there is a no ligan in my protein structure

[@DweipayanG]

Create a box around entire protein as it should fit entire protein … its called blind docking

[@md.nazimuddin4772]

Please make a video on gmx_MMPBSA.

[@user-sq8zs5ux2j]

Hi If you can help me, when i rurn the command to calculate the h-bonds ( gmx hbond -s MD.tpr -f MD_center.xtc -num hb.xvg), I can't find anything (the file doesn't contain h-bonds). I use gromacs 2023, and i anlyzed the RMSD,RMDF, Rg successfully.

[@DweipayanG]

Strange !!

[@user-sq8zs5ux2j]

@@DweipayanG I have seen two new files in the output files (are mdout.mdp and MD_prev.cpt). Maybe this is where the problem started.

[@DweipayanG]

You can change input files in same command and try

[@user-sq8zs5ux2j]

@@DweipayanG Hi, It remains the same problem.

[@dhimanshukumar8739]

1:04:39 I am using gromacs 2023.2 and it is not showing gpu selected , it was showing CUDA enabled initially and even the fans of gpu turn on while NVT run command , can you suggest what could the problem be ? My graphic card is rtx2060

[@youssrafatima3671]

Hiw to calculat sasa in gtomacs

[@anuamirtha477]

The Swiss param website is not opening

[@hasankachal11]

try old version

[@NurArshad]

Can I use this tutorial for protein-protein complex?

[@DweipayanG]

Nope

[@NurArshad]

@@DweipayanG may I know which tutorial I should use for protein-protein complex?

[@youssrafatima3671]

Sir pls how to calculate sasa and pca in the gromacs pls

[@DweipayanG]

According to the GROMACS documentation²³, you can use the **gmx sasa** command to compute the solvent accessible surface area (SASA) for your system. You need to specify a selection for the surface calculation with the **-surface** option, and optionally additional selections with the **-output** option. You can also use various options to control the output files, such as **-o** for total area, **-odg** for estimated solvation free energy, **-or** for average area per residue, and **-oa** for average area per atom. For example, you can use: `gmx sasa -s md.tpr -f md_traj.trr -o sasa.xvg -or res-sasa.xvg -surface "Protein" -output "Protein"` to calculate the SASA of a protein in a trajectory file⁴. Alternatively, you can use the older command **g_sas**, which has similar options¹. For example, you can use: `g_sas -s md.tpr -f md_traj.xtc -o sasa.xvg -or res-sasa.xvg` to calculate the SASA of a system in an xtc file¹. Source: Conversation with Bing, 19/05/2023 (1) gmx sasa - GROMACS 2018 documentation. manual.gromacs.org/documentation/2018/onlinehelp/gmx-sasa.html. (2) gmx sasa - GROMACS 2023.1 documentation. manual.gromacs.org/current/onlinehelp/gmx-sasa.html. (3) How to compute the Solvent Accessible Surface Areas (SASA) with GROMACS .... www.compchems.com/how-to-compute-the-solvent-accessible-surface-areas-sasa-with-gromacs/. (4) How to calculate solvent accessible surface (SASA)? - FAQS.TIPS. faqs.tips/post/how-to-calculate-solvent-accessible-surface-sasa.html.

[@manisha380]

Hello Dr, Hi have many doubts can I get your email I’d please

[@DweipayanG]

[e-mail]

[@suchandrimasadhukhan2185]

It is taking a long time for nvt equlibration....what should I do!?...while running the cursor us also stop blinking! Please it's urgent kindly let me know

[@DweipayanG]

Well it does take time , try doin 2 ns simulations first wait for it to get done , if things go well then proceed with longer simulation

[@mantibiswas2307]

I have a problem with mol2 file, when I parameterize through SwissParam, its provide a failure report, and when I fix this, no details were shown, but it's still showing error.... How do I fix this?

[@user-fp4fl8bs3p]

use SMILES-form for your ligand