VMD-L Mailing List

From: Gumbart, James C (gumbart_at_physics.gatech.edu)
Date: Tue Nov 13 2018 - 19:54:19 CST

Thanks for the shoutout. We did do coordination of cobalamin by histidine, similar to what is done for heme in the CHARMM force field. I don’t think we put any extra care into it though. As always, I would start with what published examples have done and choose a path based on time and accuracy constraints.

Best,
JC

On Nov 13, 2018, at 9:37 AM, Brian Radak <brian.radak_at_gmail.com<mailto:brian.radak_at_gmail.com>> wrote:

Despite the wide interest, I would say this is still a largely unresolved problem.

Indeed, GAFF is, in my recollection, a rather deterministic procedure. CGenFF at least gives penalty scores when it believes it is doing poorly, but there really isn't much recourse in that case other than to do a detailed quantum chemical study of the molecule (e.g. using FFTK). To the best of my knowledge, using a covalent ligand immediately jumps your workflow to the detailed quantum chemical study, since neither GAFF nor CGenFF are really prepared for that.

There was a recent paper on the parameterization of cobalamines from the Gumbart Lab - maybe that will offer some best practices? I know that they used FFTK. At the very least you could probably get a hold of their workflow.

HTH,
BKR

On Tue, Nov 13, 2018 at 2:14 AM Francesco Pietra <chiendarret_at_gmail.com<mailto:chiendarret_at_gmail.com>> wrote:
Hi Brian:
I understand your point, which was also my suspicion, though not clearly declared. Covalent ligands are no rarity, actually pharma is paying much attention to them, under the hope that they reside longer than non-covalent ligands at the active site.I remember vaguely of some simulation work with cytochrome c. If I am correct, that was a case of covalent ligands. But who did that, and with which ff?

It seems to be easier with amber ffs, since gaff is compatible with them, although gaff is speedy to provide a ff for the ligand as if it were a straightforward affair.

cheers
francesco

On Mon, Nov 12, 2018 at 7:19 PM Brian Radak <brian.radak_at_gmail.com<mailto:brian.radak_at_gmail.com>> wrote:
Francesco,

I'm not sure that what you are attempting is well-advised. I don't think CGenFF was ever intended for covalent linkage to the protein force field and I don't think there is any automated path to do so. There is some correspondence between CHARMM36 and CGenFF types and you could notionally convert CGenFF interactions by matching, but my understanding is that this has never been suggested by the MacKerell group or others.

You will probably have to find a detailed procedure from the literature to follow. Unfortunately I have no experience with covalently linked ligands, so I have no tips to offer there.

HTH,
BKR



On Mon, Nov 12, 2018 at 12:51 PM Vermaas, Joshua <Joshua.Vermaas_at_nrel.gov<mailto:Joshua.Vermaas_at_nrel.gov>> wrote:
If residue 1 in the patch is supposed to be HSP, why are you setting the type/charge of a likely non-existent atom?
 "ATOM 2NE2 NG2R52 -0.133"

This should probably be ATOM 1NE2, shouldn't it?

-Josh


On 2018-11-12 02:02:08-07:00 owner-vmd-l_at_ks.uiuc.edu<mailto:owner-vmd-l_at_ks.uiuc.edu> wrote:

Hi:
I am trying to get bonding between protein HSP NE2 and an organic ligand carbon, while imposing CGenFF atom types on both sides.
PRES ZAHI 1.449 ! patch for ligand to HSP bonding
                      ! Patch must be 1-HSP and 2-ZPN
                      ! use in patch statement
                      ! follow with AUTOgenerate ANGles DIHEdrals command
GROUP !
ATOM 2C11 CG311 0.332 !
ATOM 2C10 CG314 0.199 !
ATOM 2H15 HGA1 0.09 !
ATOM 2C9 CG2D2 0.127 !
ATOM 2C8 CG2O5 0.333 ! CD2--NE2--CE1
GROUP ! /
ATOM 2CD2 CG2R51 0.219 ! C11--C10--C9--C8
ATOM 2NE2 NG2R52 -0.133! |
ATOM 2CE1 CG2DC1 0.349 ! H15
DELETE ATOM 2H16
DELETE ATOM 1HE2
BOND 2C10 1NE2
IMPR NE2 CD2 CE1 C10
IMPR NE2 CE1 CD2 C10
However, the new atom names are only accepted for the ligand, not for the protein, which conserved the original atom types CPH1 NR3 CPH2 for CD2 NE2 CE1, with bonding between C10 (CG314) and NE2 (NR3). pdb file shows zero coordinated for CD2 NE2 CE1 on the ligand residue.
All that because I am trying to avoid parameterization for unusual bonds, such as between CG314 and NR3, although I understand that with atom type NG2R52 for NE2 a cascade of problems would arise on the protein side.
So, which is the best way to associate CGenFF to charmm36?
thanks
francesco pietra