Hi Michael,
there was a thread on this in the mailing list a few weeks back:
http://archive.ambermd.org/202303/0114.html My response seems not to have
been archived, so I copied it here:
my experience here may be outdated, but the stability issues you mention
are (or were some years ago) typical for MD simulations of protonated
phosphates. As you describe, the imbalance between electrostatics and vdW
repulsion is the issue here. A normal hydroxyl H does not need a LJ center,
because it is sufficiently protected by both the O-LJ volume plus, and this
is key, the relatively stiff angle bending in e.g. C-C-O groups, so the H
is kept away from the heavy atoms three bonds away. In contrast, a
phosphate has
O-P-O angle terms which are softer plus relatively high charges on both H
and O, so the collapse you describe between atoms 1 and 4 in a O-P-O-H
substructure can occur. The ad hoc solution of giving the H non-zero vdW
parameters will make the simulation stable (most likely) but in principle
you'd be on the hook to show that this still describes the phosphate group
well in the environment you simulate it in. The cowardly solution would be
to claim that the phosphate has pK around 7 anyway and in the presence of
all those nucleic acid associated metal cations, you may as well simulate
it deprotonated.
Dave also suggested stiffening the O-P-O or P-O-H angles which also should
prevent such instabilities from happening.
Kind Regards,
Thomas
On Mon, Jun 5, 2023 at 8:08 PM Michael Bruist via AMBER <amber.ambermd.org>
wrote:
> My group is trying to model RNAs with 5’-phosphates. We are getting crashes
> that may indicate a problem for the force fields in terminalphos.lib
> (Amber18) and terminalphos.LJbb-RNA (Amber20). Both have a problem in that
> bond angles with the protonated oxygen are not maintained during
> minimization or pmemd runs. See attached 10-frame movie for a failure in
> minimization.
>
> Attached are the following files for our attempts to use this in AMBER20:
>
> GMP_failure.mp4 a 10-frame movie showing the failure of the 5’ phosphate
> in the upper left.
> tleap_commands.txt
> TLS1_clipped_K.inmin
>
> I also wanted to attach the parm file, but its size prohibited this
> message from being accepted. I am including a link to a Google drive
> folder.
>
> https://drive.google.com/drive/folders/1EvhLYvcV5DkpDGNmbQR7B5-R8Pd_yeTp?usp=sharing
>
> For the future, what is the best way to provide access to such large files?
>
> Thanks for your help.
>
> Mike Bruist
> --
> Michael F. Bruist
> Professor of Biochemistry
> Department of Chemistry and Biochemistry
> 215-596-8530 (University City office)
> 610-649-5474 (home, "COVID office")
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
>
--
*Dr. Thomas Steinbrecher*
Principal Scientist CADD
Roche Pharma Research and Early Development
Roche Innovation Center Basel
F. Hoffmann-La Roche Ltd
Bldg. 092/3.92
Grenzacherstrasse 124
4070 Basel
Switzerland
Phone +41 61 682 1319
mailto: thomas.steinbrecher.roche.com
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Mon Jun 05 2023 - 23:30:02 PDT
