[Chimera-users] molecular dynamics with phosphates: monobasic form unstable?

[Geoffrey Sametz]

Thanks for your help! Unfortunately, in my hands, this as well produces a
phosphate that blows up, both for your exact example and also as applied to
my cases. I tried uninstalling SwissSidechain as well, but to no effect.

Generally, the phosphate becomes agitated with severe conformations and
steric clashes (e.g. you see things like one O bonding to another O to form
a three-membered OPO ring, but with a hydrogen superimposed on an O). The
agitation increases across the molecule until it "explodes" into pieces.

I'm going to work with the well-behaved dibasic phosphate for now.... I'm
just recording my experience here in the email record in case it helps
someone else.

On Sat, Mar 30, 2019 at 4:44 PM Elaine Meng <meng at cgl.ucsf.edu> wrote:

> Hi Geoffrey,
> I don’t think anybody has tried the Chimera dynamics tool with
> phosphorylated sidechains.  The minimization/MD tools in Chimera are fairly
> limited and slow (no cutoffs or sophisticated handling of long-range
> electrostatics, no detailed control over residue parameters) compared to
> dedicated programs like GROMACS and AMBER, so most detailed research with
> MD, as opposed to brief explorations of flexibility or structure cleanup,
> would use one of those dedicated packages instead.
>
> I can answer the part about protonation and adding charges in Chimera, but
> whether it will attain stability in simulation may be a separate matter.
>
> Before you add hydrogens, just change the automatically assigned atom type
> of the oxygen you wish to protonate to O3.  I can see for example with the
> TPO in 1guf chain A that the three terminal oxygens are automatically given
> type O3-
>
> open 6guf
> delete ~protein
> delete ~:.a
> disp :tpo
> focus :tpo
> labelopt info idatmType
> label :tpo
>
> (… select the oxygen you want to change with Ctrl-click)
>
> setattr a idatmType O3 sel
> label sel
>
> addh
> addcharge
> (...TPO is now estimated as charge -1, OK)
>
> I tried 100 steps steepest descent minimization, selecting a zone within
> 4A of TPO and allowing only those atoms to move, and it didn’t move much.
>
> I hope this helps,
> Elaine
> -----
> Elaine C. Meng, Ph.D.
> UCSF Chimera(X) team
> Department of Pharmaceutical Chemistry
> University of California, San Francisco
>
> > On Mar 30, 2019, at 11:31 AM, Geoffrey Sametz <sametz at udel.edu> wrote:
> >
> > I am having my students model dipeptides where one residue is a
> phosphorylated serine or threonine. Molecular dynamics with the dibasic
> phosphate works fine. However, the student NMR data for their dipeptides is
> acquired at low pH, so I would like them to be able to model the monobasic
> form. Unfortunately, all my attempts at creating a monobasic form have
> resulted in the molecule "blowing up" in MD, first by crazily shaking the
> phosphate as if it wants to dislodge the proton, and then the entire
> molecule until it fragments.
> >
> > I have tried building these from scratch by various methods (e.g. those
> listed in
> http://plato.cgl.ucsf.edu/pipermail/chimera-users/2012-January/007068.html
> ) as well as using SwissSidechain and mutating residues. I have tried
> exporting as a .pdb, opening in PyMOL to make sure everything looks OK,
> resaving as .pdb and importing PyMOL's version.
> >
> > I have also used a protein from PDB that had a TPO residue assigned, and
> snipped it down to a dipeptide.For both this manner of construction, and
> for building the dipeptide from scratch with SwissSidechain, Chimera
> interprets SwissSidechain's TPO (pThr monobasic) and SEP (pSer monobasic)
> as their dibasic forms (TPO2 and SEP2 respectively). PyMOL interprets these
> structures with the correct level of protonation, however.
> >
> > Is there a known issue with Chimera and treatment of [-OPO3H]-1 groups,
> or have I managed to make the same error across multiple build methods?
> >
> > --
> > Dr. Geoffrey Sametz
> > QDH 104
> > Department of Chemistry and Biochemistry
> > University of Delaware
> > sametz at udel.edu
> > (302) 831-3621
> > _______________________________________________
> > Chimera-users mailing list: Chimera-users at cgl.ucsf.edu
> > Manage subscription:
> http://plato.cgl.ucsf.edu/mailman/listinfo/chimera-users
>
>

-- 
Dr. Geoffrey Sametz
QDH 104
Department of Chemistry and Biochemistry
University of Delaware
sametz at udel.edu
(302) 831-3621
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