Re: QMMM Question

From: McGuire, Kelly (mcg05004_at_byui.edu)
Date: Thu Feb 14 2019 - 14:06:11 CST

Sorry, didn't hit reply all. Here is what I said:

Thank you for the advice. I wonder if it would be acceptable to use PM7 just for a general idea of how the ligand interacts with the active, and render dynamic bonds. But for thermodynamical properties, don't do Qmmm, but freeze all non-relevant atoms and treat relevant atoms with DFT, including some explicit waters nearby.

PM7 should give good coordination geometries, even for divalent copper according to some literature I've read. It's the energy calculations that I worry about. Semiempirical methods probably don't give very accurate energy results for the transition metals.

What I am hoping to see is that the copper can form a covalent bond with these sidechain groups. But, if the electronic calculations are incorrect with seimiempirical, how can I trust any dynamic bonds that VMD renders between the sidechains and the copper?

Kelly L. McGuire

PhD Candidate

Biophysics

Department of Physiology and Developmental Biology

Brigham Young University

LSB 3050

Provo, UT 84602

________________________________
From: Brian Radak <brian.radak_at_gmail.com>
Sent: Thursday, February 14, 2019 12:04:50 PM
To: namd-l; McGuire, Kelly
Subject: Re: namd-l: QMMM Question

Hi Kelly,

In general, I don't think there is a high opinion of minimal basis semi-empirical methods for modeling multivalent ions in biological systems. A d-orbital augmented method (e.g. MNDO/d or AM1/d) might do ok, but the parameters probably don't exist and you would likely end up calibrating to WFT/DFT. Personally, I would benchmark PM7 (or whatever) in this fashion anyway, probably looking at ligand exchange energies, otherwise you risk a harsh dismissal by a journal referee.

Cheers,
BKR

P.S. The QM/MM implementation in NAMD may also have trouble with highly charged quantum regions due to the way long-range electrostatics are handled. The ligands that coordinate your ion might matter a lot.

On Thu, Feb 14, 2019 at 12:28 PM McGuire, Kelly <mcg05004_at_byui.edu<mailto:mcg05004_at_byui.edu>> wrote:

  I am trying to get binding energies and heats of formation of a divalent copper binding to 4 sidechains in a protein. I have been doing QM/MM using PM7, but I'd like to get some opinions from more experienced computational biophysicists/chemists. For something like divalent copper, is it really worth treating my QM region with PM7? What results/values can I really trust from this? Or do you recommend a higher theory, like DFT, to apply to my QM region, even though that would slow down the computation significantly, but give better results?

Kelly L. McGuire

PhD Candidate

Biophysics

Department of Physiology and Developmental Biology

Brigham Young University

LSB 3050

Provo, UT 84602

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