Just curious, are there anything special about the individual monomers?
Charged, for instance? If so, what are the sizes of the monomers and how
many formal charges does each monomer have (also the signs)? Are they
explicit solvent simulations? Sorry, you might have said earlier.
As for "stable" tetramer, mind let us know the condition (salt
concentration, co-solvent) under which the tetramer was stable
experimentally? How much interface we are talking about (relative to the
total surface)? After dissociated, were the individual monomers stable? As
for your "first simulation of 110ns", did you change anything?
It is a bit odd to have supposedly stable tetramer falling apart in a few
ns.
yong
-----Original Message-----
From: owner-amber.scripps.edu [mailto:owner-amber.scripps.edu] On Behalf Of
David Cerutti
Sent: Tuesday, January 22, 2008 11:14 AM
To: amber.scripps.edu
Subject: Re: AMBER: Has anyone seen a protein fall apart due to PBCs?
Oh, we're certain that the protein is falling apart along that interface.
I've dealt with all sorts of imaging problems in the past, so I know when
they pop up. This is an issue of the protein tetramer RMSD becoming 1.0A
greater than the average RMSD of its subunits, then 1.5A, then 3.0A, then
5.0A, and finally rocketing to >20A (but doing so smoothly over a period
of a few ns).
Thanks to all who have replied, I will look into the restrained
equilibration more closely. However, given that the separation happened
110ns into the first simulation, I don't think that this was the issue.
In that first simulation, there were indications of the protein
moving towards its ultimate separation in the first 30ns, but these later
went away and came back around 80ns into the simulation, gradually
building until the separation at 110ns.
A simulation of a small-molecule liganded form of the same tetrameric
protein, known experimentally to be more stable than the unliganded
tetramer, has been solidly together over a simulation of 180ns and
counting. The equilibration was the same in both cases. Experimentally,
this tetrameric protein is known to form a very stable tetramer even
without the ligand, but again binding the ligand is known to further
stabilize the tetramer.
Dave
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Received on Wed Jan 23 2008 - 06:07:33 PST
