Hi Ning,
You are right. After checking several previous AMBER forum discussions (such as
http://archive.ambermd.org/201301/0468.html and
http://archive.ambermd.org/201208/0095.html), it will be prudent to keep a small r3 (or even small r2 value) if the box size is relatively small compared to the molecule. Or enlarging the box dimensions could be an option.
Maybe more experts in "periodic boundary conditions" can give suggestions on this topic. Congratulations on the "r3=44" setup working and being reproducible!
Best regards,
Zhenn
_____________________
Zhen Li<
http://lizhen62017.wixsite.com/home>, Ph.D.,
The Merz Research Group<
http://merzgroup.org>,
Michigan State University,
Cleveland Clinic.
________________________________
From: ning <ningdancer.163.com>
Sent: Monday, April 28, 2025 6:16 AM
To: Li, Zhen <lizhen6.chemistry.msu.edu>; AMBER Mailing List <amber.ambermd.org>
Subject: Re:Re: [AMBER] Fw: Request help: how manipulate the prmtop file to add exclusion force
Dear Zhen,
Thanks for your guidance about how to use the NMR restraint in MD. And I found an interesting question that when placed the NMR distance restraint between two ligands, I can easily noticed that two ligands quickly seperated to each orther in early time, however, after a short time simulation (about 50ns), two ligands aggregated again. Here are my input files:
###this is the pmemd input ###
&cntrl
imin=0,
irest=1, ntx=5,
nstlim=50000000, dt=0.002,
ntc=2, ntf=2,
ntpr=5000, ntwx=5000, ntwr=5000,
cut=8.0,
ntb=2,
ntp=1,taup=2.0, pres0=1.0,
ntt=3, gamma_ln=2.0, temp0=300.0,
iwrap=1, ioutfm=1,
nmropt=1,
/
&wt type='REST', istep1=0, istep2=0, value1=1.0, value2=1.0 /
&wt type='END' /
DISANG=restraint_pot_bottomn.RST
/
#### this is the restraint file: restraint_pot_bottomn.RST ####
&rst
iat=-1,-1,0
igr1=11,10,16,82,46,100,57
igr2=238,140,147,187,233,213,177
r1=5.0, r2=20.0, r3=66.0, r4=80.0, rk2=100.0, rk3=100.0,
nstep1=0, nstep2=0,
&end
Another weird phenomenon is that if reduced r3 value to 40, the NMR restraint can keep well through the whole MD simulation. Some important things I nearly forget to list, my simulaiton used the AMBER24, gaff force field and opc water model (It just a small case I want to test). And the PBC box dimensions are around 72A*69A*70A after NPT refinement. For this kind of restraint failure, I suppose it might be related with PBC box? Because small value of r3 can work very well (I've repeated this setting more than two times.) I don't know what happened here. If you have any suggestion, please let me know. Thanks so much for your time. I really appreciate it.
Best regards,
Ning
At 2025-04-15 20:23:19, "Li, Zhen via AMBER" <amber.ambermd.org> wrote:
>Hi Ning,
>
>Have you tried the rst feature in cpptraj? https://amberhub.chpc.utah.edu/rst/ . You may also find it on page 712 of the AMBER24 use manual.
>
>After doing what this tutorial said, you will be able to apply NMR restraints to the ligands by making the end of your MD input look like this (assuming you are using pmemd).
>
>...<other MD inputs like nstlim, ntpr, etc.,>...
> nmropt=1,
>/
>&wt type='END'
>/
>DISANG=output
>/
>&ewald
>nfft1=48, nfft2=48, nfft3=48,
>/
>
>Wish all the best!
>
>
>_____________________
>
>Zhen Li<http://lizhen62017.wixsite.com/home>, Ph.D.,
>
>The Merz Research Group<http://merzgroup.org>,
>
>Michigan State University,
>
>Cleveland Clinic.
>
>________________________________
>From: ning via AMBER <amber.ambermd.org>
>Sent: Tuesday, April 15, 2025 7:13 AM
>To: amber maillist <amber.ambermd.org>
>Subject: [AMBER] Fw: Request help: how manipulate the prmtop file to add exclusion force
>
>
>
>
>Sorry to forget to point out that MG1, MG2, MG3 are ligands name.
>
>
>
>
>Ning
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>
>-------- Forwarding messages --------
>From: "ning via AMBER" <amber.ambermd.org>
>Date: 2025-04-15 19:09:45
>To: "amber maillist" <amber.ambermd.org>
>Subject: [AMBER] Request help: how manipulate the prmtop file to add exclusion force
>Hi Amber experts,
> I hope this email find you going well. Recently, I tried to simulate a protein receptor with multiple ligands in water system by using Amber24. However, these ligands can aggregate together due to they own a little hydrophobicities. So, I would like to add a external force to push away them each other, or emliminate themselves some kind of interactions, meanwhile keep the interaction with receptor protein. I think that way maybe provide an equal opportinuty for each ligands to bind with receptor.
>
> Acutually, I had tried to modify the prmtop file by the addExclusions function in ParmED software, like this:
>parm com.prmtop
>addExclusions :MG1 :MG2
>addExclusions :MG2 :MG3
>addExclusions :MG1 :MG3
>outparm com_exclu.prmtop
>Then, it give me a new topology file named com_exclu.prmtop. But, in real simualtion case (I used ff19SB for protein, gaff for ligands, and OPC for water molecules.), this action doesn't work. These ligands still aggregate with each other. So how do I manipulate this topology file to reach this goal. Please help me! Thanks so much for any suggestions.
>
>
>Best,
>Ning
>
>_______________________________________________
>AMBER mailing list
>AMBER.ambermd.org
>https://urldefense.com/v3/__http://lists.ambermd.org/mailman/listinfo/amber__;!!HXCxUKc!xn_12x6jV1RMW43Kx7HTInmgOnE-Yf0rtN1AuXYra_p0dUuKsrb9xnhjk4womsPh6ODgmJEozrQxurNcG4x8LAA$
>_______________________________________________
>AMBER mailing list
>AMBER.ambermd.org
>https://urldefense.com/v3/__http://lists.ambermd.org/mailman/listinfo/amber__;!!HXCxUKc!xn_12x6jV1RMW43Kx7HTInmgOnE-Yf0rtN1AuXYra_p0dUuKsrb9xnhjk4womsPh6ODgmJEozrQxurNcG4x8LAA$
>_______________________________________________
>AMBER mailing list
>AMBER.ambermd.org
>http://lists.ambermd.org/mailman/listinfo/amber
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Mon Apr 28 2025 - 14:30:02 PDT
