VMD-L Mailing List

From: Smith, Harper E. (smith.12510_at_buckeyemail.osu.edu)
Date: Wed Oct 07 2020 - 15:28:52 CDT

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>
Sent: Wednesday, October 7, 2020 3:48 PM
To: Smith, Harper E. <smith.12510_at_buckeyemail.osu.edu>
Cc: vmd-l_at_ks.uiuc.edu <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