AMBER Archive (2007)

Subject: RE: AMBER: Time step & non-bonded interactions updating

From: Francesco Pietra (chiendarret_at_yahoo.com)
Date: Sun Dec 16 2007 - 10:36:46 CST

Hi Ross:
Thanks, and I must deeply apologize. Since I started using DOCK, I shifted to
Chimera as viewer/analyzer, while the conclusions about protein instability
were drawn from VMD, with which I have little familiarity. Therefore, I badly
misinterpreted VMD's responses.

When correctly examined with Chimera, the first 500ps production (where all
restraints were for the first time removed from the protein complex) is quite
OK as far as the transmembrane protein and its hydrated POPC membrane
environment are concerned. The input was:

prod1 complex_pop box80x80
 &cntrl
  imin=0, irest=1, ntx=5,
  nstlim=250000, dt=0.002,
  cut=10, ntb=2, ntp=1, taup=2.0,
  ntc=2, ntf=2,
  ntpr=5000, ntwx=5000,
  ntt=3, gamma_ln=2.0,
  temp0=300.0,
 /

What has much changed (and was partly the cause of my misinterpretation) is the
docking of the ligand. While the ligand is still about in the same region of
the pore as seen with DOCK, proximity of protein residues to the ligand is
different. Within 2.6A, completely different residues from what occurred with
DOCK amber-scoring (which works under GB). While I am comforted by Pr Brozell
indication to carry out Amber MD on the docked model, my problem is whether
proximity alone is a rough indication of affinity. In fact, I am unable to find
a way with Amber9 to calculate free energies of interactions (I already posted
a question about this /\G calculation with explicit environment: no suggestion
arrived).

That said, may I ask:

Is it sound now to add to above production with new input by shortening the
time step and lengthening taup, or should production be started ex novo?

Thanks
francesco

--- Ross Walker <ross_at_rosswalker.co.uk> wrote:

> Hi Francesco,
>
> Amber 9 updates the pair list automatically as needed - there is no need to
> change it unless you specifically want backwards compatibility with earlier
> versions of Amber. Without seeing some output around the region where you
> describe "having problems of protein stability" it is hard to offer specific
> advise.
>
> However, I would try reducing the restraint weight to something like 5.0.
> You might also want to increase the value of taup to 5.0 or so. Also I have
> no experience with membrane simulations but I think you may need anisotropic
> pressure control. Perhaps other can chime in here.
>
> A time step of 1.8 to 1.5 fs may also help.
>
> All the best
> Ross
>
> /\
> \/
> |\oss Walker
>
> | HPC Consultant and Staff Scientist |
> | San Diego Supercomputer Center |
> | Tel: +1 858 822 0854 | EMail:- ross_at_rosswalker.co.uk |
> | http://www.rosswalker.co.uk | PGP Key available on request |
>
> Note: Electronic Mail is not secure, has no guarantee of delivery, may not
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>
> > -----Original Message-----
> > From: owner-amber_at_scripps.edu
> > [mailto:owner-amber_at_scripps.edu] On Behalf Of Francesco Pietra
> > Sent: Saturday, December 15, 2007 10:40
> > To: Amber
> > Subject: AMBER: Time step & non-bonded interactions updating
> >
> > I am having problems of protein stability (in a POPC membrane) during
> > equilibration and MD although the min heat density equil
> > analyses imitated from
> > tutorial A3 were OK.
> >
> > I suspect that the time-step 0.002 (see for example the in
> > file below) is
> > giving the problems (Minimization was carried out without
> > shake and heating
> > along the method of tutorial A3)
> >
> > density equilibration
> > &cntrl
> > imin=0, irest=1, ntx=5,
> > nstlim=25000, dt=0.002,
> > cut=10, ntb=2, ntp=1, taup=1.0,
> > ntc=2, ntf=2,
> > ntpr=500, ntwx=500,
> > ntt=3, gamma_ln=2.0,
> > temp0=300.0,
> > ntr=1,
> > restraintmask=":77-521 | :POP_at_O2, P1, O3, O4, O1, C15, C11,
> > N, C12, C13, C14"
> > restraint_wt=32,
> > /
> >
> > Before changing to dt=0.001, may I ask about updating
> > non-bonded interactions,
> > which might also be relevant. As far as I understand from the
> > manual of Amber9,
> > updating non-bonded interactions with a *.in file like above
> > occurs by default
> > to security values. In descriptions from Amber8 non-bonded
> > interactions were
> > set to be updated every 10 time steps. I would like to have
> > this precise
> > condition. Much obliged for instructing me how to set that in Amber9.
> >
> > francesco pietra
> >
> >
> >
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