Hi,
From my understanding, 'same as c3-c -o' indicates that this parameter is derived from 'c3-c -o' when obtained using GAFF with AMBER atom types. I’m not entirely sure, but parmchk2 might not identify replaced parameters when using the AMBER protein force field with GAFF atom types, and there should be 'ATTN' remarks in the generated frcmod file.
In your case, since the ligand contains an imine group, setting AMBER atom types for CYS part and GAFF2 atom types for ligand part seems to be a practical approach. In this way, you have protein force field parameters for CYS and the atoms between the custom residue and flanking amino acids, while the parameters for the CYS-ligand linkage and ligand are adopted from GAFF2. For atomic charge generation, apply charge constraints to peptide bond atoms same to ff14SB. And run a preliminary MD simulation to check if the resulting custom residue conformation is reasonable.
Hopefully, other experienced people can chime in.
Regards,
Zijian
________________________________
发件人: Javier O Sanlley-hernandez <jsanlleyhernandez.UCSD.EDU>
发送时间: 2024年8月28日 1:00
收件人: Huang ZiJian <Hzj-0820.outlook.com>; AMBER Mailing List <amber.ambermd.org>; Daniel Roe <daniel.r.roe.gmail.com>
主题: Re: [AMBER] Custom AA residue missing parameters
Hello,
Thanks for the feedback, but in the meantime allow me to elaborate on what I am trying to do since I am sure there’s a way around it with the current version of AMBER I am using. Either way I really appreciate the help and feedback!
I am trying to generate parameters for a custom amino acid residue where a cysteine is bonded to my ligand of interest. This ligand contains an imine group (sp2 nitrogen) not recognized by amber atom types. According to the tutorials and documentation I proceeded with the gaff atom types for generating the subsequent .ac and.prepin files.
The issue that I am having has to do with using tleap to generate the topology file of the custom amino acid bonded to the rest of the protein. I am getting a missing bond and angle parameter error for the atoms between the custom residue and flanking amino acids.
When I go back to the tutorials and documentation to look at the example frcmod files, I noticed that there is a “same as c3-c -o , penalty score= 0.0“ for gaff frcmod files generated from .ac or .prepin file with amber type atoms. I do not see however this remark for the ff14sb frcmod files I generated for gaff type atoms. Is this expected? Or am I missing something for generating the frcmod files.
Hopefully this makes my problem a bit more clearer, and again thank you so much for the help!
From: Huang ZiJian <Hzj-0820.outlook.com>
Date: Monday, August 19, 2024 at 9:39 PM
To: Javier O Sanlley-hernandez <jsanlleyhernandez.UCSD.EDU>, AMBER Mailing List <amber.ambermd.org>
Subject: 回复: [AMBER] Custom AA residue missing parameters
Hi,
In AMBER 22, GAFF2 version is 2.11. While GAFF2 is version 2.20 now in AMBER 23 and 24, which has the "c5" atom type and related parameters. It is better to use newest AmberTools.
Regards,
Zijian
________________________________
发件人: Javier O Sanlley-hernandez via AMBER <amber.ambermd.org>
发送时间: 2024年8月20日 3:59
收件人: Daniel Roe <daniel.r.roe.gmail.com>; AMBER Mailing List <amber.ambermd.org>
主题: Re: [AMBER] Custom AA residue missing parameters
Hello!
Thanks for getting back to me, so I tried doing the same procedure but with atom types as gaff2 instead of gaff and instead of missing bond and angle parameter errors I get missing vdW parameters for c5 atoms (see below).
Let me know if this helps,
/software/repo/moleculardynamics/amber/2022/bin/teLeap: Error!
For atom (.R<LIG 145>.A<C5 9>) could not find vdW (or other) parameters for type (c5)
/software/repo/moleculardynamics/amber/2022/bin/teLeap: Error!
For atom (.R<LIG 145>.A<C7 12>) could not find vdW (or other) parameters for type (c5)
/software/repo/moleculardynamics/amber/2022/bin/teLeap: Error!
For atom (.R<LIG 145>.A<C6 13>) could not find vdW (or other) parameters for type (c5)
/software/repo/moleculardynamics/amber/2022/bin/teLeap: Error!
For atom (.R<LIG 145>.A<C9 25>) could not find vdW (or other) parameters for type (c5)
/software/repo/moleculardynamics/amber/2022/bin/teLeap: Error!
For atom (.R<LIG 145>.A<C10 28>) could not find vdW (or other) parameters for type (c5)
From: Daniel Roe <daniel.r.roe.gmail.com>
Date: Monday, August 19, 2024 at 1:47 PM
To: Javier O Sanlley-hernandez <jsanlleyhernandez.ucsd.edu>, AMBER Mailing List <amber.ambermd.org>
Subject: Re: [AMBER] Custom AA residue missing parameters
Hi,
I think if you generate parameters with parmchk2 you have to load
leaprc.gaff2 (not leaprc.gaff).
-Dan
On Mon, Aug 19, 2024 at 3:39 PM Javier O Sanlley-hernandez via AMBER
<amber.ambermd.org> wrote:
>
> Hello,
>
> I am trying to prepare a custom amino acid residue where a cysteine is covalently bound to a ligand for MD simulations.
>
> I followed the steps outlined in the amber custom amino acid residue<https://urldefense.com/v3/__https://ambermd.org/tutorials/basic/tutorial5/__;!!Mih3wA!DdYTs-Y8rRKU0RMfoxgVLpx9dtjiDGTm1_dAxRTCqak1Wp7_u4yiuLYqz9PWLWeZG58OjY87TR-9L3d5i7FAEXvlkFgCkQ$ > and tert-leucine tutorials<https://urldefense.com/v3/__https://carlosramosg.com/amber-custom-residue-parameterization__;!!Mih3wA!DdYTs-Y8rRKU0RMfoxgVLpx9dtjiDGTm1_dAxRTCqak1Wp7_u4yiuLYqz9PWLWeZG58OjY87TR-9L3d5i7FAEXu9IAdOnw$ > supplemented by the documentation in the Amber 22 manual to generate the appropriate files. Commands are included below.
>
> The issue I’m having is that upon generating the necessary .prepin and .frcmod files, I cannot generate the .prmtop topology file when I run tleap using a pdb with the custom amino acid flanked by adjacent residues as input (Error: missing bond and angle parameters). Alternatively, running tleap with the uncapped residue pdb as input does not give me any errors.
>
> I also noticed that running the desc command on the custom residue shows ‘null’ for the head atom, even though both head and tail atoms were defined in the .mc file.
>
> Thanks in advance for your help,
>
> Javier Sanlley
> UC San Diego
>
> ---
>
> Amber22 commands:
>
> antechamber -i lig_capped.pdb -fi mol2 -o lig_capped.ac -fo ac -c bcc -rn LIG -at gaff
>
> prepgen -i lig_capped.ac -o lig_capped.prepin -f ac -m lig_capped.mc -rn LIG
>
> parmchk2 -i lig_capped.ac -o lig_capped.frcmod -f ac -a Y
> (no ATTN remarks)
>
> tleap input file
>
> Source leaprc.protein.ff19SB
> Source leaprc.gaff
>
> Loadamberprep lig_capped.prepin
> Loadamberparams lig_capped.frcmod
>
> LIG = loadpdb lig_uncapped.pdb or lig_flanked.pdb
>
> Saveoff LIG lig_uncapped.lib
> Saveamberparm LIG lig_uncapped.prmtop lig_uncapped.rst7
>
> Tleap error messages:
>
> Error: Could not find bond parameter for atom types: C - n
> for atom C at position -14.036000, 22.450000, -31.516000
> and atom N at position -14.822000, 21.367000, -31.604000.
>
> Error: Could not find bond parameter for atom types: c - N
> for atom C at position -13.727000, 20.025000, -33.379000
> and atom N at position -12.634000, 19.262000, -33.506000.
> Checking for angle parameters.
>
> Error: Could not find angle parameter for atom types: O - C - n
> for atom O at position -12.834000, 22.442000, -31.769000,
> atom C at position -14.036000, 22.450000, -31.516000,
> and atom N at position -14.822000, 21.367000, -31.604000.
>
> Error: Could not find angle parameter for atom types: C - n - hn
> for atom C at position -14.036000, 22.450000, -31.516000,
> atom N at position -14.822000, 21.367000, -31.604000,
> and atom H at position -15.804000, 21.448000, -31.377000.
>
> Error: Could not find angle parameter for atom types: C - n - c3
> for atom C at position -14.036000, 22.450000, -31.516000,
> atom N at position -14.822000, 21.367000, -31.604000,
> and atom CA at position -14.366000, 20.032000, -31.985000.
>
> Error: Could not find angle parameter for atom types: CX - C - n
> for atom CA at position -14.678000, 23.764000, -31.044000,
> atom C at position -14.036000, 22.450000, -31.516000,
> and atom N at position -14.822000, 21.367000, -31.604000.
>
> Error: Could not find angle parameter for atom types: o - c - N
> for atom O at position -14.193000, 20.727000, -34.274000,
> atom C at position -13.727000, 20.025000, -33.379000,
> and atom N at position -12.634000, 19.262000, -33.506000.
>
> Error: Could not find angle parameter for atom types: c - N - H
> for atom C at position -13.727000, 20.025000, -33.379000,
> atom N at position -12.634000, 19.262000, -33.506000,
> and atom H at position -12.326000, 18.698000, -32.725000.
>
> Error: Could not find angle parameter for atom types: c - N - CX
> for atom C at position -13.727000, 20.025000, -33.379000,
> atom N at position -12.634000, 19.262000, -33.506000,
> and atom CA at position -11.821000, 19.222000, -34.715000.
>
> Error: Could not find angle parameter for atom types: c3 - c - N
> for atom CA at position -14.366000, 20.032000, -31.985000,
> atom C at position -13.727000, 20.025000, -33.379000,
> and atom N at position -12.634000, 19.262000, -33.506000.
>
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> https://urldefense.com/v3/__http://lists.ambermd.org/mailman/listinfo/amber__;!!Mih3wA!DdYTs-Y8rRKU0RMfoxgVLpx9dtjiDGTm1_dAxRTCqak1Wp7_u4yiuLYqz9PWLWeZG58OjY87TR-9L3d5i7FAEXtftVnmmQ$<https://urldefense.com/v3/__http:/lists.ambermd.org/mailman/listinfo/amber__;!!Mih3wA!DdYTs-Y8rRKU0RMfoxgVLpx9dtjiDGTm1_dAxRTCqak1Wp7_u4yiuLYqz9PWLWeZG58OjY87TR-9L3d5i7FAEXtftVnmmQ$><https://urldefense.com/v3/__http:/lists.ambermd.org/mailman/listinfo/amber__;!!Mih3wA!DdYTs-Y8rRKU0RMfoxgVLpx9dtjiDGTm1_dAxRTCqak1Wp7_u4yiuLYqz9PWLWeZG58OjY87TR-9L3d5i7FAEXtftVnmmQ$%3chttps:/urldefense.com/v3/__http:/lists.ambermd.org/mailman/listinfo/amber__;!!Mih3wA!DdYTs-Y8rRKU0RMfoxgVLpx9dtjiDGTm1_dAxRTCqak1Wp7_u4yiuLYqz9PWLWeZG58OjY87TR-9L3d5i7FAEXtftVnmmQ$%3e>
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber<
https://urldefense.com/v3/__http:/lists.ambermd.org/mailman/listinfo/amber__;!!Mih3wA!EmI8K9xtt-cME0zIsB54X4V0ejXst9ddnEWEc52BnCKvzraWtV-ls2FcchiwKOMvi37USS30ws2Lxg5HcA17yIrFKg$>
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Fri Aug 30 2024 - 01:00:02 PDT
