VMD-L Mailing List

From: Smith, Harper E. (smith.12510_at_buckeyemail.osu.edu)
Date: Thu Oct 08 2020 - 10:04:11 CDT

Hi everyone,

Thank you for sharing your invaluable insight. I am lucky this community is so active and supportive.

I will follow Robin's advice to draw before-and-after structures while perusing the topology and parameter files. Hopefully, I can reach the same conclusion as JC and Aaron. In the future, we may need parameters for more complex molecules -- when this happens, I will follow advice from Axel and JC by contacting experts for guidance.

Best,
Harper Smith
________________________________
From: owner-vmd-l_at_ks.uiuc.edu <owner-vmd-l_at_ks.uiuc.edu> on behalf of Aaron Oakley <aarono_at_uow.edu.au>
Sent: Wednesday, October 7, 2020 9:13 PM
To: vmd-l_at_ks.uiuc.edu <vmd-l_at_ks.uiuc.edu>
Subject: Re: vmd-l: Glu-Lys Isopeptide Bond Parameters?

Your new patch (Let's call it EKAM) can be made by analogy with DKAM and will look something like this…

Notice the change in atom names (e.g. 1CG etc) but not types (e.g. CT2).

PRES EKAM -0.18 ! Patch to create AMide bond between Glu (E) and Lys (K), based on DKAM
DELETE ATOM 1OE2 ! follow with AUTOgenerate ANGLes DIHEdrals command
DELETE ATOM 2HZ2
DELETE ATOM 2HZ3
ATOM 1CG CT2 -0.18 ! Neutralize CG. This causes total -0.18 charge above.
GROUP
ATOM 1CD C 0.51 ! from NMA
ATOM 1OE1 O -0.51
GROUP
ATOM 2NZ NH1 -0.47 ! From NMA
ATOM 2HZ1 H 0.31
ATOM 2CE CT2 -0.02 ! Transfered from NMA by summing
ATOM 2HE1 HA2 0.09 ! deleted hydrogen charge into parent.
ATOM 2HE2 HA2 0.09 ! Apply standard charges to now-nonpolar hydrogens.

BOND 1CD 2NZ
IMPR 2NZ 1CD 2CE 2HZ1
IMPR 1CD 1CG 2NZ 1OE1
IC 1CB 1CG 1CD 2NZ 0.0000 0.00 180.00 0.00 0.0000
IC 1CG 2NZ *1CD 1OE1 0.0000 0.00 180.00 0.00 0.0000
IC 2CD 2CE 2NZ 1CD 0.0000 0.00 180.00 0.00 0.0000
IC 2CE 1CD *2NZ 2HZ1 0.0000 0.00 180.00 0.00 0.0000
IC 1CG 1CD 2NZ 2CE 0.0000 0.00 180.00 0.00 0.0000

–ĺ

On 8 Oct 2020, at 7:28 am, Smith, Harper E. <smith.12510_at_buckeyemail.osu.edu<mailto:smith.12510_at_buckeyemail.osu.edu>> wrote:

Hi Josh,

Thank you for drawing my attention to the DKAM patch in the standard distribution, and I will follow your advice when applying a patch to two residues (I have only applied them to one residue before). This is almost what I need -- unfortunately, it must be between GLU/LYS instead of ASP/LYS.

After searching through all patches involving glutamate (I grepped "patch" and "GLU" everywhere in the most recent C36 distribution), I do not see mention of my isopeptide bond.

Could you please elaborate about how I might change the patch by analogy? Is there a more standard way to proceed for someone with weak chemical intuition?

Best,
Harper Smith
________________________________
From: Josh Vermaas <joshua.vermaas_at_gmail.com<mailto:joshua.vermaas_at_gmail.com>>
Sent: Wednesday, October 7, 2020 3:48 PM
To: Smith, Harper E. <smith.12510_at_buckeyemail.osu.edu<mailto:smith.12510_at_buckeyemail.osu.edu>>
Cc: vmd-l_at_ks.uiuc.edu<mailto:vmd-l_at_ks.uiuc.edu> <vmd-l_at_ks.uiuc.edu<mailto:vmd-l_at_ks.uiuc.edu>>
Subject: Re: vmd-l: Glu-Lys Isopeptide Bond Parameters?

Hi Harper,

The first thing I'd check is to see if the DKAM patch is what you are looking for (its in stream/prot/toppar_all36_prot_modify_res.str in a standard CHARMM36 distribution), which based on the description in the file is meant to describe the situation similar (ASP-LYS staple), and is a blessed part of the CHARMM36 force field. You'd apply it via a patch to your current protein. I like to use the DISU patch in the psfgen userguide as the example syntax of how patches are applied to two residues, keeping in mind that the order matters in your case (ASP/GLU first, then the LYS). If it needs to be a Glu, the first step would be to check if it exists somewhere else in the stream files (I don't know them by heart), or do the changes by analogy.

-Josh

On Wed, Oct 7, 2020 at 1:09 PM Smith, Harper E. <smith.12510_at_buckeyemail.osu.edu<mailto:smith.12510_at_buckeyemail.osu.edu>> wrote:
Hi mailing list,

I'd like to use CHARMM parameters to simulate a system containing a Glu-Lys isopeptide bond, but I am unsure how to generate the parameters.

I have seen guides for parameterizing small molecules using FFTK, but is this appropriate for a covalent bond between two side chains?

There is a guide by Robin Betz about making isopeptide bond parameters for AMBER (https://robinbetz.com/blog/2016/11/28/parameterizing-an-isopeptide-bond/-c$>) -- but Dr. Kohlmeyer pointed out in 2014 that converting AMBER parameters to CHARMM is not straightforward (https://www.ks.uiuc.edu/Research/vmd/mailing_list/vmd-l/23636.html$>). Is this still true?

In your opinion, could you give me a sense of the difficulty of this problem? Can a non-expert like me generate publication-quality parameters for this covalent modification?

Best,
Harper Smith