Re: [AMBER] GPI-anchor protein cleavage

From: Aditya Padhi <>
Date: Wed, 17 Jun 2015 06:06:11 +0530

Dear Jason.

Thank you very much for your detailed reply. I am not new to MD simulations
and have run simulations before quite extensively.

I wanyed to know if there are any specific forcefields or options in amber
that I could try as for my protein of interest and the GPI anchor proteins,
the structures are not available and they are mostly membrane proteins.

As you suggested, I have to ask a really specific question to study what I
want. QM/MM MD and umbrella sampling would be helpful though.

Thank you very much for your suggestions.
On 16-Jun-2015 8:06 pm, "Jason Swails" <> wrote:

> On Tue, Jun 16, 2015 at 12:49 PM, Aditya Padhi <> wrote:
> > Dear Amber Users,
> >
> > I am working on a protein, which is known to cleave few GPI-anchor
> proteins
> > (Glycosylphosphatidylinisotol). Also, I know that there are several other
> > candidate GPI-anchor proteins which may or may not be cleaved by my
> protein
> > of interest. I was wondering, if there is any tool/method in Amber using
> > which I can atleast get some preliminary information on these.
> >
> You really need a more specific question. QM/MM can be used to probe
> chemical reactions in enzymes. You can combine that with PMF methods like
> umbrella sampling to get free energies along a reaction coordinate. You
> can also run classical MD on your system and look at particular
> interactions that may be occurring near the active site (and see if there
> are differences between those that *do* cleave and those that *don't*).
> Again, the types of simulations you would run would depend very heavily on
> what you ultimately hope to learn through your simulations.
> The QM studies are probably not "preliminary" studies, since they will
> require a lot of time to set up, run, and learn how to perform effectively
> if you've never done it before.
> ​
> > The 3D structure of my protein of interest and most of the GPI-anchor
> > proteins is not available. I was therefore wondering if there is any such
> > tools/methods available that I am missing.
> >
> ​This makes it a very challenging problem. You may be able to use homology
> modeling to develop a starting conformation, but that is certainly not
> guaranteed to work and it would take a fair amount of time to learn how to
> do it.
> ​HTH,
> Jason​
> --
> Jason M. Swails
> BioMaPS,
> Rutgers University
> Postdoctoral Researcher
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Received on Tue Jun 16 2015 - 18:00:02 PDT
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