AMBER Archive (2003)

Subject: Re: AMBER: Simulation of small protein

From: Carlos Simmerling (carlos_at_csb.sunysb.edu)
Date: Thu Oct 23 2003 - 17:59:58 CDT

Hi Robert,
I guessed it was villin since there aren't so many 36 residue proteins.
It is fairly compact so I am not sure why your RMSD goes
up so fast, is it well equilibrated? equilibration in GB can be
hard since there isn't anything to damp out initial fluctuations.
I'm not too familiar with villin though, maybe Yong Duan can comment?
The SA term may do the same, just damp out any initial poor contacts
etc.

As to the best force field to use, I am not sure on that either. Parm99
and even 94 (though less so) seem to be significantly overstabilizing alpha
conformations bu since villin is helical maybe that's actually better for
getting it to fold-again maybe Yong can comment on that. For real
dynamics I would expect it to be too helical, although helix extension may
be something to look for in your RMSD increase.

Try frequency filtering in mddisplay, it can help a lot with reducing the
wiggles.
Carlos

----- Original Message -----
From: "Endres, Robert G." <endresrg_at_ornl.gov>
To: <amber_at_scripps.edu>
Sent: Thursday, October 23, 2003 1:27 PM
Subject: RE: AMBER: Simulation of small protein

>
> Dear Carlos,
> its the villin headpiece which was described as a thermostable, fast
folding
> alpha-helical subdomain. I also looked at the trajectory with mddisplay:
at the beginning of the movie the structure seems a bit more open, but its
hard to tell since its just a bunch of wobbling atoms.
>
> What's a better force field - parm94, or the one you published
> in JACS on Trpcage folding? By the way, in this paper did you use GB or
GBSA?
> When I just use GB (without SA-term) it actually partially unfolds at the
beginning of trajectory (starts to open up but closes then slowly again).
>
> Robert
>
> -----Original Message-----
> From: owner-amber_at_scripps.edu on behalf of Carlos Simmerling
> Sent: Thu 10/23/2003 12:13 PM
> To: amber_at_scripps.edu
> Cc:
> Subject: Re: AMBER: Simulation of small protein
> it depends on whether you're seeing backbone changes-
> we've publsihed that there is significant overstabilization of alpha
> helix in parm99+GB. on a long time scale, all of
> our sequences increased in helical content and the
> energy dropped. Seeing this during 200ps is a bit surprising
> though.
>
> without knowing what the topology looks like it is
> hard to say whether more compact is reasonable (is it
> a rather open structure to start with?)
> Carlos
>
> ----- Original Message -----
> From: "Endres, Robert G." <endresrg_at_ornl.gov>
> To: <amber_at_scripps.edu>
> Sent: Thursday, October 23, 2003 11:52 AM
> Subject: AMBER: Simulation of small protein
>
>
> >
> > Dear AMBER users,
> >
> > After heating/equilibration of a NMR structure of a small (36 res.)
> protein with weak constraints, I was doing a short (0.2 ns) MD simulation
> (parm99.dat) at 300K with the GBSA implicit solvent model.
> > I was a bit surprised that the total energy dropped further by almost
100
> kcal/mol compared to the starting structure (close to NMR structure), and
> the ESURF term (proportional to the total surface) decreased from 17 to 12
> kcal/mol.
> > So the protein got more compact during the MD simulation. The RMSD
started
> from zero and increased to 3-5 A.
> > It seems that the protein changed quite strongly the structure during
the
> simulation. Does anyone have experience with this, i.e. is this "normal"
or
> "expected", is this a problem with the force field/solvent model or NMR
> structure?
> >
> > Many thanks for suggestions,
> >
> > Robert
> >
> >
> >
> >
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