Re: protein folding

From: Anton Arkhipov (anton_at_ks.uiuc.edu)
Date: Fri Jul 10 2009 - 10:37:29 CDT

Axel is absolutely right, the force field of the MARTINI coarse-grain
model is not suitable for simulations of protein folding (that applies
also to any other coarse-grain model at this level, as far as I know,
unless you are using a Go model or such, which biases folding
trajectories).

The reason is that the model is coarse, so specific interactions that
determine protein structure cannot be modeled precisely enough.
Therefore, even if you simulate a protein starting from its crystal
structure using such a coarse-grain model, the protein's secondary and
tertiary structure will quickly drift away from what they should be.
You can use angular, dihedral, and distance constraints to maintain
proper secondary and tertiary structure, but that will essentially
keep your protein in only one known conformation. Such trick allows
one to simulate a protein with well defined structure using the coarse-
grain models such as MARTINI, but obviously that's not what you want
for protein folding.

Like Axel said, this issue is stated very clearly in the MARTINI
papers. You also can find papers from Marrink himself and from Mark
Sansom's group, where they used MARTINI with constraints on the
protein structure to simulate, e.g., membrane proteins. Some
applications have been done in our group, where we used angular and
dihedral constraints to maintain secondary structure, and distance
constraints to maintain tertiary structure. Here are our papers that
can be of interest:

Coarse grained protein-lipid model with application to lipoprotein
particles. Amy Y. Shih, Anton Arkhipov, Peter L. Freddolino, and Klaus
Schulten. Journal of Physical Chemistry B, 110:3674-3684, 2006.

Assembly of lipoprotein particles revealed by coarse-grained molecular
dynamics simulations. Amy Y. Shih, Peter L. Freddolino, Anton
Arkhipov, and Klaus Schulten. Journal of Structural Biology,
157:579-592, 2007.

Assembly of lipids and proteins into lipoprotein particles. Amy Y.
Shih, Anton Arkhipov, Peter L. Freddolino, Stephen G. Sligar, and
Klaus Schulten. Journal of Physical Chemistry B, 111:11095-11104, 2007.

Four-scale description of membrane sculpting by BAR domains. Anton
Arkhipov, Ying Yin, and Klaus Schulten. Biophysical Journal,
95:2806-2821, 2008.

Best,

Anton.

On 10 Jul 2009, at 07:48, Axel Kohlmeyer wrote:

> On Fri, 2009-07-10 at 11:00 +0300, doty alexiou wrote:
>
>>
>> Hi.I am running an NAMD simulation of a protein(folding process)
>> using
>> the extended martini foce field.The simulation has run about 70-80
>> ns(323 k,timestep 10,PBC,in water,RMSD is about 18 till now).Up until
>> now,there is no sign of the expected secondary structure of the
>> protein.Is there any suggestion about what could be wrong or if i
>> should expect it longer?Thank u.
>
> do you have any proof that the martini force field _can_ fold
> proteins?
>
> the 2008 monticelli paper explicitly states that the secondary
> structure
> of proteins is not at all modeled, but used as input parameter and
> then
> kept fixed. so in my opinion you are currently wasting your time and
> that of your computer.
>
> cheers,
> axel.
>
>>
>>
>>
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> --
> =
> ======================================================================
> Axel Kohlmeyer akohlmey_at_cmm.chem.upenn.edu http://
> www.cmm.upenn.edu
> Center for Molecular Modeling -- University of Pennsylvania
> Department of Chemistry, 231 S.34th Street, Philadelphia, PA
> 19104-6323
> tel: 1-215-898-1582, fax: 1-215-573-6233, office-tel: 1-215-898-5425
> =
> ======================================================================
> If you make something idiot-proof, the universe creates a better
> idiot.

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