Re: AMBER: Simulating a section of a molecule

From: Carlos Simmerling <>
Date: Thu, 15 Feb 2007 13:06:50 -0500

it is well known that a particular sequence in a large protein has different
structural properties than the same sequence in a short peptide. If you
don't have the whole molecule, you probably won't have the same structure or
stability. I'm not surprised that your helix frays on the ends- the entropy
of these residues is very different when you simulate the fragment.
We published a paper last year in JMB where we obtained conformational
ensembles for fragments of the villin HP36 protein. Our simulations were
consistent with experimental data by our collaborators in which 2 of the 3
fragments lose all structure completely compared to the full protein, and 1
retains only a small amount of helix.
You might read it to seee what methods we used to make sure that the
simulations were reliable.

**Wickstrom, L., Okur, A., Song, K., Hornak, V., Raleigh, D. and Simmerling,
C., *"The Unfolded State of the Villin Headpiece Helical Subdomain:
Computational Studies of the Role of Locally Stabilized Structure"*, J. Mol.
Biol., 360:1094-1107 (2006).

On 2/15/07, Dave, Sonya <> wrote:
> Hi,
> I am trying to make a 3D structure of an alpha helix, which is part of a
> larger molecule. I'm doing it using homology modeling and refining use
> Molecular Dynamics. This isn't really an amber question, as much as
> maybe something from your experience.
> My "alpha helix ", when simulated, doesn't look like an alpha helix at
> it's ends. The middle amino acids do resemble a helix though (it's 7 a.a.
> total). I believe, in the true structure, the whole thing is a helix. Do
> you think this "improper" structure could be because I don't have the whole
> molecule? Perhaps, because the end amino acids don't have neighboring amino
> acids, They may not show proper secondary structure. I'm using explicit
> solvent. Each simulation takes quite a while, so I just wanted your opinion
> about whether I should try rerunning the simulation with more amino acids on
> each side of the helix to fix the structure. But, perhaps the problem is
> something completely different (like i'm not using a proper force field).
> Another question is, would you consider something to be a alpha helix/beta
> sheet, etc, even if programs (VMD, Chimera, DSSP, etc) don't call it one.
> Do you treat what the programs tell you as secondary structures as strictly
> correct?
> I know this isn't exactly an amber question. However, I don't have much
> experience with simulations, or structural biology in general, and don't yet
> have ready access to people who can help me on campus. But I appreciate your
> help on the issue.
> Regards,
> Sonya

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Received on Sun Feb 18 2007 - 06:07:22 PST
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