[AMBER] RE: RE: question on section 2 of MM-PBSA tutorial

From: Ross Walker <ross.rosswalker.co.uk>
Date: Fri, 16 Apr 2010 18:29:31 -0700

Hi Andrew,

> I acutally didn't understood what was the purpose for density run as
> far as it was just restrained molecular dynamics. While in some
> tutorials :
> http://ambermd.org/tutorial/polyA-polyT_New/minandmd3.html
> the constant volume molecular dynamics was performed at this stage with
> fixed biopolymer by weak restraints:
> http://ambermd.org/tutorial/polyA-
> polyT_New/amber_input_files/polyAT_wat_md1.in
> which is corresponding to heat run here:
> http://ambermd.org/tutorials/advanced/tutorial3/files/heat.in
> how different is restraintmask with force constants from such approach
> of fixed biopolymer with weak restraints as in polyAT_wat_md1.in?

There is no golden recipe for doing these simulations and many people differ
in their approaches / how cautious they are etc. Generally the polyA-polyT
tutorial was designed to be a little more conservative to make sure
newcomers didn't try to be too aggressive with their structures and wonder
why sometimes things go wrong.

In the MM-PBSA tutorial though we were probably even more conservative
because the structure here, the ras-raf complex was not necessarily the best
starting structure and I wanted to give it time to relax. The main procedure
is always:

1) Minimize. This has to be done. It could probably be done without the
restraints but since the weighting is very small, 2.0 Kcal/mol/A which is
about 1/150th of a bond strength it probably makes no difference. The
minimization is designed to remove the very high energy VDW clashes.

2) Heat / equilibrated density. This is critical for explicit solvent
simulations since Leap creates water boxes with initial densities of only
around 0.8g/cm^3. This is because it over estimates the box size to avoid
VDW clashes at the edges. If one does not equilibrate the density there will
be vacuum bubbles formed in the solvent which is very bad. However, one
cannot run NTP at low initial temperatures because the pressure calculation
is very inaccurate at low temps. This can lead to instabilities due to over
correction by the barostat. Hence one heats first and then equilibrates the
density. The key is the density of the water, the protein really doesn't
change much so it is fine to keep the restraints on. Plus they are very weak
so probably don't cause an issue.

> Btw also I a little bit don't understand the purpose of NMR restraints
> usage in the heat.in? There are no references to NMR in the text.

The NMR restraints are not actual restraints. They are being used to control
the thermostat. They linearly scale the target temperature from 0.1 to 300.0
over 25000 steps. Otherwise with Langevin dynamics the temperature would
just jump to 300K within a few hundred steps which could lead to

> Aslo in MM/PBSA tutorial no minimization without restraints of the
> whole system was performed as here:
> http://ambermd.org/tutorial/polyA-
> polyT_New/amber_input_files/polyAT_wat_min2.in

As above it probably doesn't matter. Especially as the restraints are VERY

> So at least I plan to add minimization without restraints to the
> computations in MM-PBSA tutorial, before heat.

You can do that, it certainly won't do any harm.
> PS I am just try to fit MM PBSA tutorial and DNA tutorial parameters to
> each other.

I understand. I wouldn't focus overly on the details though since as I say
there is no perfect solution and the purpose of minimization, heating /
equilibration is just to get to a point where the system is stable but has
moved sufficiently far from the starting conditions that the results are not
dependent on it. That is, if I was to vary the minimization / heating /
equilibration procedure slightly it should not show up in the final results.
If it does then enough data has not been gathered for converged statistics
or not enough time was allowed for the simulation to relax away from the
starting structure.

I hope that makes sense.

All the best

|\oss Walker

| Assistant Research Professor |
| San Diego Supercomputer Center |
| Tel: +1 858 822 0854 | EMail:- ross.rosswalker.co.uk |
| http://www.rosswalker.co.uk | http://www.wmd-lab.org/ |

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Received on Fri Apr 16 2010 - 19:00:02 PDT
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