Hi Cesar,

The IdoA ring exists in a delicate equilibrium between the 1C4-2So-4C1 ring
conformations, and transitions between conformations are relatively slow
(microsecond time-scale). Neither the previous charges nor the newest
charges reliably reproduce the ring populations. I've attached the prep
files used to create the IdoA conformations on the website (IdoA_ALL.prep),
as well as the most recent version of glycam.

If you describe your hypothesis (reason for running the simulations), I may
be able to help you design an experiment to test it. For example, a
collaborator synthesized compounds and collected NMR data to determine how
sulfation around IdoA affects the ring conformations. Using NMR data and
MD, we were able to determine the ratio of ring conformations in each
compound. Then, I ran MD simulations of each compound where the ring was
restrained in each conformation. This allowed us to study the
intramolecular interactions at each conformation and avoided the issue of
properly sampling IdoA ring conformations in one long simulation. Here's a
link to the publication:

Please let me know if you have any other questions.


On Wed, Jul 26, 2017 at 11:23 AM, Cesar Avila <[log in to unmask]>

> Hi David,
> thanks for your reply. I would be glad to give the new parameter set a
> shot on my system. I ran a quick simulation (10 ns) of the
> LIdopA[2S](2SO)a1-4DGlcpNS[6S]a1-4-OME using the residues OMe, UYS and
> 2uA (along with the proper sulfates) and adjusted the charges to those of
> 2uA2. Still I saw that most of the time the Irudonic ring would spend most
> of the time on a chair conformation. I imagined that I was missing some
> parameters other than the charges when building the system from 2uA. So I
> would deeply appreciate if along with the new parameter set you could also
> send me the prep files for 2uA2, so I can asses  the impact on the
> conformation of my molecule.
> Best regards,
> Cesar
> ----- Mensaje original -----
> De: "David Thieker" <[log in to unmask]>
> Para: [log in to unmask]
> Enviados: MiƩrcoles, 26 de Julio 2017 11:26:11
> Asunto: Re: Residue on parm file from gag builder missing in
> GLYCAM_06j-1.prep
> Hi Cesar,
> We have finished developing GLYCAM06k and are currently testing the files
> to avoid any bugs. The new version of the IdoA residue type will be
> included in this update, which should be released in the next week or so.
> If you need the files sooner, I can send what we have. That would also help
> us with the testing.
> Just let me know how urgently you need them.
> Best,
> David
> On Tue, Jul 25, 2017 at 6:35 PM, Cesar Avila <[log in to unmask]>
> wrote:
> > Hello all,
> > I have recently prepared topology, parameter and configuration files for
> a
> > heparin disaccharide using the GAG builder on the website as follows
> >
> > LIdopA[2S](2SO)a1-4DGlcpNS[6S]a1-4-OME
> >
> > Notice that for the irudonic ring I have selected to use the 2S0
> > configuration. As a result, I get a parm7 and pdb file with the irudonic
> > residue named 2uA2 (instead of the 2uA residue that gets generated for a
> > chair configuration). I want to use tleap to build my system from
> scratch,
> > without using the parm7 file. Unfortunately, I cannot find the 2uA2
> residue
> > anywhere in the prep files that come with amber (or in the glycam
> webpage).
> > I have noticed that the charges on the atoms is different between 2uA and
> > 2uA2. I was wondering if you could help me find the prep file that is
> > currently used by the GAG builder, so I can use it with tleap.
> > Best regards,
> >
> > Cesar
> >
> --
> David F. Thieker
> PhD Candidate
> Biochemistry and Molecular Biology
> Complex Carbohydrate Research Center
> University of Georgia, Athens, GA

David F. Thieker
PhD Candidate
Biochemistry and Molecular Biology
Complex Carbohydrate Research Center
University of Georgia, Athens, GA