Re: Applying conformational constraints during simulation

Date: Tue Oct 23 2007 - 08:51:25 CDT

I'm looked at the TMD function in the user guide, and it has a target
reference file right?
- I took that to mean the simulation is aimed at directing the protein
towards/away from the reference conformation and this reference is fixed.

However, what I am seeking is pulling on a protein with steered MD while
maintaining an additional constraints on its conformation. This means that
I have a *moving* reference to which the protein in the simulation is
expected to conform to.
^ More technical terms: I wish to apply a constraint u_c to keep the
protein in proper shape while leaving the rotational and translational
freedoms intact. This requires some sort of fitting of a set of reference
coordinates to the current orientation of the protein, then calculating
forces on the atoms towards this transformed reference coordinates. For
simplicity I would have chosen the measure fit procedure in vmd but I
don't think I can access that routine during simulation.

I guess that I can set up TMD targets on various points along the reaction
coordinate, but it does remove rotational freedom.

The second question is directed at a simplistic alternative. I have a
protocol which alternates between pulling the protein @ 5 A/ns for 0.5
Angs then equilibriates the result before pulling further. The actual
probem is that a loosely bonded N-terminal strand detaches during several
pulling steps and does not repair itself during equilib.
I suspect that it is the force on the COM coordinate of the protein) which
causes this diassociation, but cannot be sure if this is the case or the
pulling itself is causing the disruption. *The detached N-terminal shifts
COM in the direction of pulling, and decreases the force on the binding
site residues.

If I can turn the protein into a rigid body (or place a conformational
constraint) and move it around, it might help to tell me the exact cause.

I thought about implementing a tcl script to copy this transformation. It
will take a fair amount of work which is already done in the sense that I
would rather figure out how if there's a way to import the VMD "measure
fit" routine.
About pulling the protein slower:
The current speed, 5 A/ns, already takes a long time due to the size of the
system. I don't think I can drop it further (~1 A/ns absolute?) considering
the computational resources available.
Quoting Victor Ovchinnikov <ovchinnv_at_MIT.EDU>:
> Poker,
> The TMD function in NAMD should be able to do exactly this.  See the
> user's guide on pages 72-73.  A word of caution: when run in parallel,
> some NAMD binaries give errors in TMD.  There are posts on this problem
> on this list.  I do not know whether this issue has been resolved yet.
> I'm not sure what you mean by your second question. Could you clarify?
> Best,
> Victor
> On Tue, 2007-10-23 at 13:08 +1000, wrote:
> > I have a protein which I am pulling from a binding site by SMD (center
> of
> > mass coordinates). In order to keep the protein properly folded I am
> > planning on applying a coordinate-based constraint based on aligning
> its
> > backbone reference to the protein's current position in the system.
> > Is this possible in NAMD? There's an equivalent process in the latest
> > CHARMM (recorded in cons.doc under RMSD constraints) - is there a way
> to
> > align a reference set of coordinates during the simulation?
> >
> > ---
> > Also, is it possible to freeze the coordinates of the ligand and still
> move
> > it during simulation?
> >
> > Poker.
> >
> > ----------------------------------------------------------------
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> >
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