AMBER Archive (2006)

Subject: Re: AMBER: Simulating proteins with calcium ion

From: Thomas Cheatham (tec3_at_utah.edu)
Date: Thu Dec 07 2006 - 21:23:26 CST

> I am trying to simulate a protein-protein complex with a calcium ion
> (Ca2+) at the binding interface. Energy minimizations on the initial
> crystal structure without explicit solvent lead to displacement of Ca2+,
> even though the ion is restrained. I searched the Amber achieve and

Despite other "expert" commentaries to the contrary, I am a little
confused by what you are seeing which could in turn explain what you are
seeing.

In general, minimization will not lead to significant movement as the
underlying potential energy surface is very rough and the AMBER
minimization algorithms are simple (as they should be), such that
minimization will move to the nearest local minima (i.e. move atoms very).
The exception to this is conjugate gradient, which because of the jump
size, could cross local minima and find nearby local minima; even still
the motion is small: The bottom line is, close local minima will be
found and large scale motion is unlikely.

If you have funny structures, for example a chain in the middle of a ring,
minimization will not move the chain outside the ring. It will instead
find a nearby minima (still at high energy but still a minima) that has
the chain still in the ring. Unless a soft-core potential is implemented
(see work by van Gunsteren, Pitera, Simmerling, etc) atoms cannot
generally move through other atoms due to the stiff inverse r**12 wall.

Now, let's dissect what you are seeing from the information provided. An
"ion" is placed, nominally a Ca2+ ion at some binding interface. The ion
is restrained, yet it "moves" during minimization. No explicit solvent is
present.

If the ion is indeed restrained, it will not move in minimization, even
given a large overlap/penalty. Therefore I would assume that the
surroundings (i.e. protein) are moving. Even still, minimization will not
move things very much (as local minima are prevalent) so I am confused
that everything is moving. Are you running dynamicss? If there is
problem with the simulation?

If this was constant pressure / explicit solvent, with restraints or
belly, the pressure algorithms could shift the relative positions of
molecules (leading to a situation as you describe) but from your e-mail,
this is in-vacuo and only the ion is restrained.

Short answer: We need more info and it is unusual for minimization to move
things as much as you suggest, especially if restraints are applied.
There could be bugs or there could be problems. Also, from your e-mail it
is not clear how far things are moving...

-- tom

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