VMD-L Mailing List

From: Gumbart, JC (gumbart_at_physics.gatech.edu)
Date: Sun Apr 03 2022 - 15:41:48 CDT

There was literally no way to do it with the water-interaction approach for a number of atoms in that molecule, so we just had to do what we could. We did indeed fix some hydrogen charges according to standard CHARMM style.

With regards to the QM method, I don’t think you need to stick with HF, necessarily? Play around and see how sensitive the numbers are to this choice. You need to decide what you’re optimizing for, which will be the real test of whether it worked or not.

Best,
JC

On Apr 1, 2022, at 3:52 AM, Daniel Fellner <dfel694_at_aucklanduni.ac.nz<mailto:dfel694_at_aucklanduni.ac.nz>> wrote:

Oh great, thanks! I didn't realise RESP was suitable for deriving CHARMM-compatible partial charges. I did notice FFTK has a RESP option now but I thought it was just for AMBER.

I assume the procedure is to put static restraints on the aliphatic and aromatic hydrogens not adjacent to a heteroatom (as per CHARMM protocol) and to any atoms you don't need to optimise? I gave it a try just now, and it does a good job for most atoms, though I do notice some unphysical charges on the buried atoms. I guess I'll set these with NPA first.

Regarding the QM level of theory, should I stick to the default HF/6-31G* for both the RESP and NPA calculations? My molecule is neutral and contains only C, H, N, F, O atoms unlike the metal complexes in your paper.

Thanks again for your help,

Daniel Fellner BSc(Hons)
PhD Candidate
School of Chemical Sciences
University of Auckland
Ph +64211605326

On Fri, 1 Apr 2022 at 04:51, Gumbart, JC <gumbart_at_physics.gatech.edu<mailto:gumbart_at_physics.gatech.edu>> wrote:
With regards to your first question, yes, absolutely it helps. But if an atom is completely buried, it’s definitely less sensitive to the water interactions, but not completely immune. The danger though is that it ends up as a “dumping ground” for excess charge while the more accessible atoms get optimized. Note that RESP suffers from the same problem. We discussed such challenges in this paper: https://urldefense.com/v3/__https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980237/__;!!DZ3fjg!uW9n7HGV2JD_EpE38mCRaA80w4wG8g6DTBHS1VvPeMHDJHMZbje9BWSIoSMGveUJLw$

We ultimately settled on a combination of RESP and Natural Population Analysis, with the latter for the buried charges.

Best,
JC

On Mar 30, 2022, at 3:13 AM, Daniel Fellner <dfel694_at_aucklanduni.ac.nz<mailto:dfel694_at_aucklanduni.ac.nz>> wrote:

Just had a few questions about charge optimisation for a difficult substrate.

If the atom in question is entirely solvent-inaccessible but has hydrogens attached, does the inclusion of target data from those hydrogens aid in fitting the occluded atom? I've seen this done in the EtOH tutorial but have read conflicting information.

As for occluded atoms with no hydrogens attached, how can these be optimised? The highest penalties in my compound are on entirely occluded (SASA <0.020 nm^2/mol) atoms. Is there any sense including them in the charges to be optimised without any target data?

Daniel Fellner BSc(Hons)
PhD Candidate
School of Chemical Sciences
University of Auckland
Ph +64211605326