AMBER Archive (2009)

Subject: Re: [AMBER] Simulation short peptide and protein interaction

From: Rilei Yu (
Date: Thu Sep 03 2009 - 07:22:10 CDT

Dear David,

Thanks for your recommendation about that paper. I have read that paper. I ever tried using md to refine the docked complex a short peptide (12 residues) and its receptor. After 3 ns second, I can find the orientation slightly move. After supperposing it with the crystal structure (complex of this peptide). I find the orientation become worse that the origial docked one. As a short peptide, I have to run 10 or 20 ns to reach the refine purpose?
Or more? Do you have such experience, if it needs more than 50 ns, we may cannot afford to using md to refine the complex.

Rilei Yu

--- 09年9月2日,周三, case <> 写道:

发件人: case <>
主题: Re: [AMBER] Simulation short peptide and protein interaction
收件人: "AMBER Mailing List" <>
日期: 2009年9月2日,周三,下午8:15

On Tue, Sep 01, 2009, Rilei Yu wrote:
> I want to carry out md on a small peptide (ligand, with 12 residues) and
> protein (receptor) system. I want to simulation the interaction whole
> process, namely, from the process of the ligand enter the pocket of the
> protein to it completely accommodated by the receptor. Do anyone have
> such experience? Can we use md to carry out this intention? How much
> time it needs? As far as I know, the association rate for this short
> peptide with its receptor is very slow. Now, I have docked the peptide
> to the door of the pocket.

I think you are being unrealistically ambitious.  Even for a small, rigid
ligand, following the equilibrium process of binding is a real challenge; see,
for example:

%A O. Guvench
%A D.J. Price
%A C.L. Brooks, III
%T Receptor rigidity and ligand mobility in trypsin-ligand complexes
%J Proteins
%V 58
%P 407-417
%D 2004

To do what you describe for a 12-residue peptide ligand is way beyond what is
currently feasible with all atom models.

You should ask yourself what you are hoping to learn from such an
exercise.  It may be that a coarse-grained model would be a better choice;
or it may that you could scale back your ambitions and tackle a part of
the overall problem at a detailed level.  Start with calculations that are
similar to those you see described in the existing literature.

...good luck...dac

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